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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease</title><author><name sortKey="Schott, Jonathan M" sort="Schott, Jonathan M" uniqKey="Schott J" first="Jonathan M." last="Schott">Jonathan M. Schott</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Crutch, Sebastian J" sort="Crutch, Sebastian J" uniqKey="Crutch S" first="Sebastian J." last="Crutch">Sebastian J. Crutch</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Carrasquillo, Minerva M" sort="Carrasquillo, Minerva M" uniqKey="Carrasquillo M" first="Minerva M." last="Carrasquillo">Minerva M. Carrasquillo</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Uphill, James" sort="Uphill, James" uniqKey="Uphill J" first="James" last="Uphill">James Uphill</name><affiliation><nlm:aff id="aff3">Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Shakespeare, Tim J" sort="Shakespeare, Tim J" uniqKey="Shakespeare T" first="Tim J." last="Shakespeare">Tim J. Shakespeare</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Ryan, Natalie S" sort="Ryan, Natalie S" uniqKey="Ryan N" first="Natalie S." last="Ryan">Natalie S. Ryan</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Yong, Keir X" sort="Yong, Keir X" uniqKey="Yong K" first="Keir X." last="Yong">Keir X. Yong</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Lehmann, Manja" sort="Lehmann, Manja" uniqKey="Lehmann M" first="Manja" last="Lehmann">Manja Lehmann</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Ertekin Taner, Nilufer" sort="Ertekin Taner, Nilufer" uniqKey="Ertekin Taner N" first="Nilufer" last="Ertekin-Taner">Nilufer Ertekin-Taner</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Graff Radford, Neill R" sort="Graff Radford, Neill R" uniqKey="Graff Radford N" first="Neill R." last="Graff-Radford">Neill R. Graff-Radford</name><affiliation><nlm:aff id="aff4">Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Boeve, Bradley F" sort="Boeve, Bradley F" uniqKey="Boeve B" first="Bradley F." last="Boeve">Bradley F. Boeve</name><affiliation><nlm:aff id="aff5">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Murray, Melissa E" sort="Murray, Melissa E" uniqKey="Murray M" first="Melissa E." last="Murray">Melissa E. Murray</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Khan, Qurat Ul Ain" sort="Khan, Qurat Ul Ain" uniqKey="Khan Q" first="Qurat Ul Ain" last="Khan">Qurat Ul Ain Khan</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Petersen, Ronald C" sort="Petersen, Ronald C" uniqKey="Petersen R" first="Ronald C." last="Petersen">Ronald C. Petersen</name><affiliation><nlm:aff id="aff5">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Dickson, Dennis W" sort="Dickson, Dennis W" uniqKey="Dickson D" first="Dennis W." last="Dickson">Dennis W. Dickson</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Knopman, David S" sort="Knopman, David S" uniqKey="Knopman D" first="David S." last="Knopman">David S. Knopman</name><affiliation><nlm:aff id="aff5">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Rabinovici, Gil D" sort="Rabinovici, Gil D" uniqKey="Rabinovici G" first="Gil D." last="Rabinovici">Gil D. Rabinovici</name><affiliation><nlm:aff id="aff6">UCSF, San Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Miller, Bruce L" sort="Miller, Bruce L" uniqKey="Miller B" first="Bruce L." last="Miller">Bruce L. Miller</name><affiliation><nlm:aff id="aff6">UCSF, San Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Gonzalez, Aida Suarez" sort="Gonzalez, Aida Suarez" uniqKey="Gonzalez A" first="Aida Suárez" last="González">Aida Suárez González</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Memory Disorders Unit, Department of Neurology, University Hospital Virgen del Rocio, Seville, Spain</nlm:aff></affiliation></author><author><name sortKey="Gil Neciga, Eulogio" sort="Gil Neciga, Eulogio" uniqKey="Gil Neciga E" first="Eulogio" last="Gil-Néciga">Eulogio Gil-Néciga</name><affiliation><nlm:aff id="aff7">Memory Disorders Unit, Department of Neurology, University Hospital Virgen del Rocio, Seville, Spain</nlm:aff></affiliation></author><author><name sortKey="Snowden, Julie S" sort="Snowden, Julie S" uniqKey="Snowden J" first="Julie S." last="Snowden">Julie S. Snowden</name><affiliation><nlm:aff id="aff8">Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Harris, Jenny" sort="Harris, Jenny" uniqKey="Harris J" first="Jenny" last="Harris">Jenny Harris</name><affiliation><nlm:aff id="aff8">Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Pickering Brown, Stuart M" sort="Pickering Brown, Stuart M" uniqKey="Pickering Brown S" first="Stuart M." last="Pickering-Brown">Stuart M. Pickering-Brown</name><affiliation><nlm:aff id="aff8">Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Louwersheimer, Eva" sort="Louwersheimer, Eva" uniqKey="Louwersheimer E" first="Eva" last="Louwersheimer">Eva Louwersheimer</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Flier, Wiesje M" sort="Van Der Flier, Wiesje M" uniqKey="Van Der Flier W" first="Wiesje M." last="Van Der Flier">Wiesje M. Van Der Flier</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Scheltens, Philip" sort="Scheltens, Philip" uniqKey="Scheltens P" first="Philip" last="Scheltens">Philip Scheltens</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Pijnenburg, Yolande A" sort="Pijnenburg, Yolande A" uniqKey="Pijnenburg Y" first="Yolande A." last="Pijnenburg">Yolande A. Pijnenburg</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Galasko, Douglas" sort="Galasko, Douglas" uniqKey="Galasko D" first="Douglas" last="Galasko">Douglas Galasko</name><affiliation><nlm:aff id="aff10">Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff11">UC San Diego/VA San Diego Healthcare System, San Diego, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Sarazin, Marie" sort="Sarazin, Marie" uniqKey="Sarazin M" first="Marie" last="Sarazin">Marie Sarazin</name><affiliation><nlm:aff id="aff12">INSERM U610, Hôpital de la Salpêtrière, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Dubois, Bruno" sort="Dubois, Bruno" uniqKey="Dubois B" first="Bruno" last="Dubois">Bruno Dubois</name><affiliation><nlm:aff id="aff13">Centre des Maladies Cognitives et Comportementales, IM2A, ICM, Paris 6 University, France</nlm:aff></affiliation></author><author><name sortKey="Magnin, Eloi" sort="Magnin, Eloi" uniqKey="Magnin E" first="Eloi" last="Magnin">Eloi Magnin</name><affiliation><nlm:aff id="aff14">Regional Memory Centre (CMRR), CHU Besançon, Besançon, France</nlm:aff></affiliation></author><author><name sortKey="Galimberti, Daniela" sort="Galimberti, Daniela" uniqKey="Galimberti D" first="Daniela" last="Galimberti">Daniela Galimberti</name><affiliation><nlm:aff id="aff15">University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy</nlm:aff></affiliation></author><author><name sortKey="Scarpini, Elio" sort="Scarpini, Elio" uniqKey="Scarpini E" first="Elio" last="Scarpini">Elio Scarpini</name><affiliation><nlm:aff id="aff15">University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy</nlm:aff></affiliation></author><author><name sortKey="Cappa, Stefano F" sort="Cappa, Stefano F" uniqKey="Cappa S" first="Stefano F." last="Cappa">Stefano F. Cappa</name><affiliation><nlm:aff id="aff16">Vita-Salute San Raffaele University, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Hodges, John R" sort="Hodges, John R" uniqKey="Hodges J" first="John R." last="Hodges">John R. Hodges</name><affiliation><nlm:aff id="aff17">University of New South Wales, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M." last="Halliday">Glenda M. Halliday</name><affiliation><nlm:aff id="aff17">University of New South Wales, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Bartley, Lauren" sort="Bartley, Lauren" uniqKey="Bartley L" first="Lauren" last="Bartley">Lauren Bartley</name><affiliation><nlm:aff id="aff17">University of New South Wales, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Carrillo, Maria C" sort="Carrillo, Maria C" uniqKey="Carrillo M" first="Maria C." last="Carrillo">Maria C. Carrillo</name><affiliation><nlm:aff id="aff18">Alzheimer's Association, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Bras, Jose T" sort="Bras, Jose T" uniqKey="Bras J" first="Jose T." last="Bras">Jose T. Bras</name><affiliation><nlm:aff id="aff19">Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name><affiliation><nlm:aff id="aff19">Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Rossor, Martin N" sort="Rossor, Martin N" uniqKey="Rossor M" first="Martin N." last="Rossor">Martin N. Rossor</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Collinge, John" sort="Collinge, John" uniqKey="Collinge J" first="John" last="Collinge">John Collinge</name><affiliation><nlm:aff id="aff3">Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mead, Simon" sort="Mead, Simon" uniqKey="Mead S" first="Simon" last="Mead">Simon Mead</name><affiliation><nlm:aff id="aff3">Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26993346</idno><idno type="pmc">4982482</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982482</idno><idno type="RBID">PMC:4982482</idno><idno type="doi">10.1016/j.jalz.2016.01.010</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002228</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002228</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease</title><author><name sortKey="Schott, Jonathan M" sort="Schott, Jonathan M" uniqKey="Schott J" first="Jonathan M." last="Schott">Jonathan M. Schott</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Crutch, Sebastian J" sort="Crutch, Sebastian J" uniqKey="Crutch S" first="Sebastian J." last="Crutch">Sebastian J. Crutch</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Carrasquillo, Minerva M" sort="Carrasquillo, Minerva M" uniqKey="Carrasquillo M" first="Minerva M." last="Carrasquillo">Minerva M. Carrasquillo</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Uphill, James" sort="Uphill, James" uniqKey="Uphill J" first="James" last="Uphill">James Uphill</name><affiliation><nlm:aff id="aff3">Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Shakespeare, Tim J" sort="Shakespeare, Tim J" uniqKey="Shakespeare T" first="Tim J." last="Shakespeare">Tim J. Shakespeare</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Ryan, Natalie S" sort="Ryan, Natalie S" uniqKey="Ryan N" first="Natalie S." last="Ryan">Natalie S. Ryan</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Yong, Keir X" sort="Yong, Keir X" uniqKey="Yong K" first="Keir X." last="Yong">Keir X. Yong</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Lehmann, Manja" sort="Lehmann, Manja" uniqKey="Lehmann M" first="Manja" last="Lehmann">Manja Lehmann</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Ertekin Taner, Nilufer" sort="Ertekin Taner, Nilufer" uniqKey="Ertekin Taner N" first="Nilufer" last="Ertekin-Taner">Nilufer Ertekin-Taner</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Graff Radford, Neill R" sort="Graff Radford, Neill R" uniqKey="Graff Radford N" first="Neill R." last="Graff-Radford">Neill R. Graff-Radford</name><affiliation><nlm:aff id="aff4">Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Boeve, Bradley F" sort="Boeve, Bradley F" uniqKey="Boeve B" first="Bradley F." last="Boeve">Bradley F. Boeve</name><affiliation><nlm:aff id="aff5">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Murray, Melissa E" sort="Murray, Melissa E" uniqKey="Murray M" first="Melissa E." last="Murray">Melissa E. Murray</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Khan, Qurat Ul Ain" sort="Khan, Qurat Ul Ain" uniqKey="Khan Q" first="Qurat Ul Ain" last="Khan">Qurat Ul Ain Khan</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Petersen, Ronald C" sort="Petersen, Ronald C" uniqKey="Petersen R" first="Ronald C." last="Petersen">Ronald C. Petersen</name><affiliation><nlm:aff id="aff5">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Dickson, Dennis W" sort="Dickson, Dennis W" uniqKey="Dickson D" first="Dennis W." last="Dickson">Dennis W. Dickson</name><affiliation><nlm:aff id="aff2">Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</nlm:aff></affiliation></author><author><name sortKey="Knopman, David S" sort="Knopman, David S" uniqKey="Knopman D" first="David S." last="Knopman">David S. Knopman</name><affiliation><nlm:aff id="aff5">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Rabinovici, Gil D" sort="Rabinovici, Gil D" uniqKey="Rabinovici G" first="Gil D." last="Rabinovici">Gil D. Rabinovici</name><affiliation><nlm:aff id="aff6">UCSF, San Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Miller, Bruce L" sort="Miller, Bruce L" uniqKey="Miller B" first="Bruce L." last="Miller">Bruce L. Miller</name><affiliation><nlm:aff id="aff6">UCSF, San Francisco, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Gonzalez, Aida Suarez" sort="Gonzalez, Aida Suarez" uniqKey="Gonzalez A" first="Aida Suárez" last="González">Aida Suárez González</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Memory Disorders Unit, Department of Neurology, University Hospital Virgen del Rocio, Seville, Spain</nlm:aff></affiliation></author><author><name sortKey="Gil Neciga, Eulogio" sort="Gil Neciga, Eulogio" uniqKey="Gil Neciga E" first="Eulogio" last="Gil-Néciga">Eulogio Gil-Néciga</name><affiliation><nlm:aff id="aff7">Memory Disorders Unit, Department of Neurology, University Hospital Virgen del Rocio, Seville, Spain</nlm:aff></affiliation></author><author><name sortKey="Snowden, Julie S" sort="Snowden, Julie S" uniqKey="Snowden J" first="Julie S." last="Snowden">Julie S. Snowden</name><affiliation><nlm:aff id="aff8">Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Harris, Jenny" sort="Harris, Jenny" uniqKey="Harris J" first="Jenny" last="Harris">Jenny Harris</name><affiliation><nlm:aff id="aff8">Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Pickering Brown, Stuart M" sort="Pickering Brown, Stuart M" uniqKey="Pickering Brown S" first="Stuart M." last="Pickering-Brown">Stuart M. Pickering-Brown</name><affiliation><nlm:aff id="aff8">Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</nlm:aff></affiliation></author><author><name sortKey="Louwersheimer, Eva" sort="Louwersheimer, Eva" uniqKey="Louwersheimer E" first="Eva" last="Louwersheimer">Eva Louwersheimer</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Flier, Wiesje M" sort="Van Der Flier, Wiesje M" uniqKey="Van Der Flier W" first="Wiesje M." last="Van Der Flier">Wiesje M. Van Der Flier</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Scheltens, Philip" sort="Scheltens, Philip" uniqKey="Scheltens P" first="Philip" last="Scheltens">Philip Scheltens</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Pijnenburg, Yolande A" sort="Pijnenburg, Yolande A" uniqKey="Pijnenburg Y" first="Yolande A." last="Pijnenburg">Yolande A. Pijnenburg</name><affiliation><nlm:aff id="aff9">Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</nlm:aff></affiliation></author><author><name sortKey="Galasko, Douglas" sort="Galasko, Douglas" uniqKey="Galasko D" first="Douglas" last="Galasko">Douglas Galasko</name><affiliation><nlm:aff id="aff10">Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff11">UC San Diego/VA San Diego Healthcare System, San Diego, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Sarazin, Marie" sort="Sarazin, Marie" uniqKey="Sarazin M" first="Marie" last="Sarazin">Marie Sarazin</name><affiliation><nlm:aff id="aff12">INSERM U610, Hôpital de la Salpêtrière, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Dubois, Bruno" sort="Dubois, Bruno" uniqKey="Dubois B" first="Bruno" last="Dubois">Bruno Dubois</name><affiliation><nlm:aff id="aff13">Centre des Maladies Cognitives et Comportementales, IM2A, ICM, Paris 6 University, France</nlm:aff></affiliation></author><author><name sortKey="Magnin, Eloi" sort="Magnin, Eloi" uniqKey="Magnin E" first="Eloi" last="Magnin">Eloi Magnin</name><affiliation><nlm:aff id="aff14">Regional Memory Centre (CMRR), CHU Besançon, Besançon, France</nlm:aff></affiliation></author><author><name sortKey="Galimberti, Daniela" sort="Galimberti, Daniela" uniqKey="Galimberti D" first="Daniela" last="Galimberti">Daniela Galimberti</name><affiliation><nlm:aff id="aff15">University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy</nlm:aff></affiliation></author><author><name sortKey="Scarpini, Elio" sort="Scarpini, Elio" uniqKey="Scarpini E" first="Elio" last="Scarpini">Elio Scarpini</name><affiliation><nlm:aff id="aff15">University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy</nlm:aff></affiliation></author><author><name sortKey="Cappa, Stefano F" sort="Cappa, Stefano F" uniqKey="Cappa S" first="Stefano F." last="Cappa">Stefano F. Cappa</name><affiliation><nlm:aff id="aff16">Vita-Salute San Raffaele University, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Hodges, John R" sort="Hodges, John R" uniqKey="Hodges J" first="John R." last="Hodges">John R. Hodges</name><affiliation><nlm:aff id="aff17">University of New South Wales, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M." last="Halliday">Glenda M. Halliday</name><affiliation><nlm:aff id="aff17">University of New South Wales, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Bartley, Lauren" sort="Bartley, Lauren" uniqKey="Bartley L" first="Lauren" last="Bartley">Lauren Bartley</name><affiliation><nlm:aff id="aff17">University of New South Wales, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Carrillo, Maria C" sort="Carrillo, Maria C" uniqKey="Carrillo M" first="Maria C." last="Carrillo">Maria C. Carrillo</name><affiliation><nlm:aff id="aff18">Alzheimer's Association, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Bras, Jose T" sort="Bras, Jose T" uniqKey="Bras J" first="Jose T." last="Bras">Jose T. Bras</name><affiliation><nlm:aff id="aff19">Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name><affiliation><nlm:aff id="aff19">Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Rossor, Martin N" sort="Rossor, Martin N" uniqKey="Rossor M" first="Martin N." last="Rossor">Martin N. Rossor</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Collinge, John" sort="Collinge, John" uniqKey="Collinge J" first="John" last="Collinge">John Collinge</name><affiliation><nlm:aff id="aff3">Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C." last="Fox">Nick C. Fox</name><affiliation><nlm:aff id="aff1">Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author><author><name sortKey="Mead, Simon" sort="Mead, Simon" uniqKey="Mead S" first="Simon" last="Mead">Simon Mead</name><affiliation><nlm:aff id="aff3">Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</nlm:aff></affiliation></author></analytic><series><title level="j">Alzheimer's & Dementia</title><idno type="ISSN">1552-5260</idno><idno type="eISSN">1552-5279</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Introduction</title><p>The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain.</p></sec><sec><title>Methods</title><p>We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study.</p></sec><sec><title>Results</title><p>We confirm that variation in/near <italic>APOE/TOMM40</italic> (<italic>P</italic> = 6 × 10<sup>−14</sup>) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, <italic>P</italic> = .0007). We found evidence for risk in/near <italic>CR1</italic> (<italic>P</italic> = 7 × 10<sup>−4</sup>), <italic>ABCA7</italic> (<italic>P</italic> = .02) and <italic>BIN1</italic> (<italic>P</italic> = .04). ORs at variants near <italic>INPP5D</italic> and <italic>NME8</italic> did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed <italic>APOE</italic> and identified three novel loci: rs76854344 near <italic>CNTNAP5</italic> (<italic>P</italic> = 8 × 10<sup>−10</sup> OR = 1.9 [1.5–2.3]); rs72907046 near <italic>FAM46A</italic> (<italic>P</italic> = 1 × 10<sup>−9</sup> OR = 3.2 [2.1–4.9]); and rs2525776 near <italic>SEMA3C</italic> (<italic>P</italic> = 1 × 10<sup>−8</sup>, OR = 3.3 [2.1–5.1]).</p></sec><sec><title>Discussion</title><p>We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Crutch, S J" uniqKey="Crutch S">S.J. Crutch</name></author><author><name sortKey="Lehmann, M" uniqKey="Lehmann M">M. Lehmann</name></author><author><name sortKey="Schott, J M" uniqKey="Schott J">J.M. Schott</name></author><author><name sortKey="Rabinovici, G D" uniqKey="Rabinovici G">G.D. Rabinovici</name></author><author><name sortKey="Rossor, M N" uniqKey="Rossor M">M.N. Rossor</name></author><author><name sortKey="Fox, N C" uniqKey="Fox N">N.C. Fox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lehmann, M" uniqKey="Lehmann M">M. Lehmann</name></author><author><name sortKey="Koedam, E L" uniqKey="Koedam E">E.L. Koedam</name></author><author><name sortKey="Barnes, J" uniqKey="Barnes J">J. Barnes</name></author><author><name sortKey="Bartlett, J W" uniqKey="Bartlett J">J.W. Bartlett</name></author><author><name sortKey="Ryan, N S" uniqKey="Ryan N">N.S. Ryan</name></author><author><name sortKey="Pijnenburg, Y A L" uniqKey="Pijnenburg Y">Y.A.L. Pijnenburg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lehmann, M" uniqKey="Lehmann M">M. Lehmann</name></author><author><name sortKey="Ghosh, P M" uniqKey="Ghosh P">P.M. Ghosh</name></author><author><name sortKey="Madison, C" uniqKey="Madison C">C. Madison</name></author><author><name sortKey="Laforce, R" uniqKey="Laforce R">R. Laforce</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ossenkoppele, R" uniqKey="Ossenkoppele R">R. Ossenkoppele</name></author><author><name sortKey="Schonhaut, D R" uniqKey="Schonhaut D">D.R. Schonhaut</name></author><author><name sortKey="Baker, S L" uniqKey="Baker S">S.L. Baker</name></author><author><name sortKey="O Neil, J P" uniqKey="O Neil J">J.P. O'Neil</name></author><author><name sortKey="Janabi, M" uniqKey="Janabi M">M. Janabi</name></author><author><name sortKey="Ghosh, P M" uniqKey="Ghosh P">P.M. Ghosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang Wai, D F" uniqKey="Tang Wai D">D.F. Tang-Wai</name></author><author><name sortKey="Graff Radford, N R" uniqKey="Graff Radford N">N.R. Graff-Radford</name></author><author><name sortKey="Boeve, B F" uniqKey="Boeve B">B.F. Boeve</name></author><author><name sortKey="Dickson, D W" uniqKey="Dickson D">D.W. Dickson</name></author><author><name sortKey="Parisi, J E" uniqKey="Parisi J">J.E. Parisi</name></author><author><name sortKey="Crook, R" uniqKey="Crook R">R. Crook</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schott, J M" uniqKey="Schott J">J.M. Schott</name></author><author><name sortKey="Ridha, B H" uniqKey="Ridha B">B.H. Ridha</name></author><author><name sortKey="Crutch, S J" uniqKey="Crutch S">S.J. Crutch</name></author><author><name sortKey="Healy, D G" uniqKey="Healy D">D.G. Healy</name></author><author><name sortKey="Uphill, J B" uniqKey="Uphill J">J.B. Uphill</name></author><author><name sortKey="Warrington, E K" uniqKey="Warrington E">E.K. Warrington</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Flier, W M" uniqKey="Van Der Flier W">W.M. van der Flier</name></author><author><name sortKey="Schoonenboom, S N" uniqKey="Schoonenboom S">S.N. Schoonenboom</name></author><author><name sortKey="Pijnenburg, Y A" uniqKey="Pijnenburg Y">Y.A. Pijnenburg</name></author><author><name sortKey="Fox, N C" uniqKey="Fox N">N.C. Fox</name></author><author><name sortKey="Scheltens, P" uniqKey="Scheltens P">P. Scheltens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snowden, J S" uniqKey="Snowden J">J.S. Snowden</name></author><author><name sortKey="Stopford, C L" uniqKey="Stopford C">C.L. Stopford</name></author><author><name sortKey="Julien, C L" uniqKey="Julien C">C.L. Julien</name></author><author><name sortKey="Thompson, J C" uniqKey="Thompson J">J.C. Thompson</name></author><author><name sortKey="Davidson, Y" uniqKey="Davidson Y">Y. Davidson</name></author><author><name sortKey="Gibbons, L" uniqKey="Gibbons L">L. Gibbons</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carrasquillo, M M" uniqKey="Carrasquillo M">M.M. Carrasquillo</name></author><author><name sortKey="Khan, Q U" uniqKey="Khan Q">Q.U. Khan</name></author><author><name sortKey="Murray, M E" uniqKey="Murray M">M.E. Murray</name></author><author><name sortKey="Krishnan, S" uniqKey="Krishnan S">S. Krishnan</name></author><author><name sortKey="Aakre, J" uniqKey="Aakre J">J. Aakre</name></author><author><name sortKey="Pankratz, V S" uniqKey="Pankratz V">V.S. Pankratz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carrasquillo, M M" uniqKey="Carrasquillo M">M.M. Carrasquillo</name></author><author><name sortKey="Barber, I" uniqKey="Barber I">I. Barber</name></author><author><name sortKey="Lincoln, S J" uniqKey="Lincoln S">S.J. Lincoln</name></author><author><name sortKey="Murray, M E" uniqKey="Murray M">M.E. Murray</name></author><author><name sortKey="Camsari, G B" uniqKey="Camsari G">G.B. Camsari</name></author><author><name sortKey="Khan, Q U" uniqKey="Khan Q">Q.U. Khan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crutch, S J" uniqKey="Crutch S">S.J. Crutch</name></author><author><name sortKey="Schott, J M" uniqKey="Schott J">J.M. Schott</name></author><author><name sortKey="Rabinovici, G D" uniqKey="Rabinovici G">G.D. Rabinovici</name></author><author><name sortKey="Boeve, B F" uniqKey="Boeve B">B.F. Boeve</name></author><author><name sortKey="Cappa, S F" uniqKey="Cappa S">S.F. Cappa</name></author><author><name sortKey="Dickerson, B C" uniqKey="Dickerson B">B.C. Dickerson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendez, M F" uniqKey="Mendez M">M.F. Mendez</name></author><author><name sortKey="Ghajarania, M" uniqKey="Ghajarania M">M. Ghajarania</name></author><author><name sortKey="Perryman, K M" uniqKey="Perryman K">K.M. Perryman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delaneau, O" uniqKey="Delaneau O">O. Delaneau</name></author><author><name sortKey="Zagury, J F" uniqKey="Zagury J">J.F. Zagury</name></author><author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Howie, B N" uniqKey="Howie B">B.N. Howie</name></author><author><name sortKey="Donnelly, P" uniqKey="Donnelly P">P. Donnelly</name></author><author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name></author><author><name sortKey="Howie, B" uniqKey="Howie B">B. Howie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name></author><author><name sortKey="Howie, B" uniqKey="Howie B">B. Howie</name></author><author><name sortKey="Myers, S" uniqKey="Myers S">S. Myers</name></author><author><name sortKey="Mcvean, G" uniqKey="Mcvean G">G. McVean</name></author><author><name sortKey="Donnelly, P" uniqKey="Donnelly P">P. Donnelly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Purcell, S" uniqKey="Purcell S">S. Purcell</name></author><author><name sortKey="Neale, B" uniqKey="Neale B">B. Neale</name></author><author><name sortKey="Todd Brown, K" uniqKey="Todd Brown K">K. Todd-Brown</name></author><author><name sortKey="Thomas, L" uniqKey="Thomas L">L. Thomas</name></author><author><name sortKey="Ferreira, M A" uniqKey="Ferreira M">M.A. Ferreira</name></author><author><name sortKey="Bender, D" uniqKey="Bender D">D. Bender</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambert, J C" uniqKey="Lambert J">J.C. Lambert</name></author><author><name sortKey="Ibrahim Verbaas, C A" uniqKey="Ibrahim Verbaas C">C.A. Ibrahim-Verbaas</name></author><author><name sortKey="Harold, D" uniqKey="Harold D">D. Harold</name></author><author><name sortKey="Naj, A C" uniqKey="Naj A">A.C. Naj</name></author><author><name sortKey="Sims, R" uniqKey="Sims R">R. Sims</name></author><author><name sortKey="Bellenguez, C" uniqKey="Bellenguez C">C. Bellenguez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bras, J" uniqKey="Bras J">J. Bras</name></author><author><name sortKey="Guerreiro, R" uniqKey="Guerreiro R">R. Guerreiro</name></author><author><name sortKey="Darwent, L" uniqKey="Darwent L">L. Darwent</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corder, E H" uniqKey="Corder E">E.H. Corder</name></author><author><name sortKey="Saunders, A M" uniqKey="Saunders A">A.M. Saunders</name></author><author><name sortKey="Strittmatter, W J" uniqKey="Strittmatter W">W.J. Strittmatter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mead, S" uniqKey="Mead S">S. Mead</name></author><author><name sortKey="Poulter, M" uniqKey="Poulter M">M. Poulter</name></author><author><name sortKey="Uphill, J" uniqKey="Uphill J">J. Uphill</name></author><author><name sortKey="Beck, J" uniqKey="Beck J">J. Beck</name></author><author><name sortKey="Whitfield, J" uniqKey="Whitfield J">J. Whitfield</name></author><author><name sortKey="Webb, T E" uniqKey="Webb T">T.E. Webb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klein, R J" uniqKey="Klein R">R.J. Klein</name></author><author><name sortKey="Zeiss, C" uniqKey="Zeiss C">C. Zeiss</name></author><author><name sortKey="Chew, E Y" uniqKey="Chew E">E.Y. Chew</name></author><author><name sortKey="Tsai, J Y" uniqKey="Tsai J">J.Y. Tsai</name></author><author><name sortKey="Sackler, R S" uniqKey="Sackler R">R.S. Sackler</name></author><author><name sortKey="Haynes, C" uniqKey="Haynes C">C. Haynes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thambisetty, M" uniqKey="Thambisetty M">M. Thambisetty</name></author><author><name sortKey="An, Y" uniqKey="An Y">Y. An</name></author><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T. Tanaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mori, E" uniqKey="Mori E">E. Mori</name></author><author><name sortKey="Lee, K" uniqKey="Lee K">K. Lee</name></author><author><name sortKey="Yasuda, M" uniqKey="Yasuda M">M. Yasuda</name></author><author><name sortKey="Hashimoto, M" uniqKey="Hashimoto M">M. Hashimoto</name></author><author><name sortKey="Kazui, H" uniqKey="Kazui H">H. Kazui</name></author><author><name sortKey="Hirono, N" uniqKey="Hirono N">N. Hirono</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Flier, W M" uniqKey="Van Der Flier W">W.M. van der Flier</name></author><author><name sortKey="Pijnenburg, Y A" uniqKey="Pijnenburg Y">Y.A. Pijnenburg</name></author><author><name sortKey="Fox, N C" uniqKey="Fox N">N.C. Fox</name></author><author><name sortKey="Scheltens, P" uniqKey="Scheltens P">P. Scheltens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crehan, H" uniqKey="Crehan H">H. Crehan</name></author><author><name sortKey="Holton, P" uniqKey="Holton P">P. Holton</name></author><author><name sortKey="Wray, S" uniqKey="Wray S">S. Wray</name></author><author><name sortKey="Pocock, J" uniqKey="Pocock J">J. Pocock</name></author><author><name sortKey="Guerreiro, R" uniqKey="Guerreiro R">R. Guerreiro</name></author><author><name sortKey="Hardy, J" uniqKey="Hardy J">J. Hardy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prokic, I" uniqKey="Prokic I">I. Prokic</name></author><author><name sortKey="Cowling, B S" uniqKey="Cowling B">B.S. Cowling</name></author><author><name sortKey="Laporte, J" uniqKey="Laporte J">J. Laporte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosenthal, S L" uniqKey="Rosenthal S">S.L. Rosenthal</name></author><author><name sortKey="Kamboh, M I" uniqKey="Kamboh M">M.I. Kamboh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pagnamenta, A T" uniqKey="Pagnamenta A">A.T. Pagnamenta</name></author><author><name sortKey="Bacchelli, E" uniqKey="Bacchelli E">E. Bacchelli</name></author><author><name sortKey="De Jonge, M V" uniqKey="De Jonge M">M.V. de Jonge</name></author><author><name sortKey="Mirza, G" uniqKey="Mirza G">G. Mirza</name></author><author><name sortKey="Scerri, T S" uniqKey="Scerri T">T.S. Scerri</name></author><author><name sortKey="Minopoli, F" uniqKey="Minopoli F">F. Minopoli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lagali, P S" uniqKey="Lagali P">P.S. Lagali</name></author><author><name sortKey="Kakuk, L E" uniqKey="Kakuk L">L.E. Kakuk</name></author><author><name sortKey="Griesinger, I B" uniqKey="Griesinger I">I.B. Griesinger</name></author><author><name sortKey="Wong, P W" uniqKey="Wong P">P.W. Wong</name></author><author><name sortKey="Ayyagari, R" uniqKey="Ayyagari R">R. Ayyagari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barragan, I" uniqKey="Barragan I">I. Barragán</name></author><author><name sortKey="Borrego, S" uniqKey="Borrego S">S. Borrego</name></author><author><name sortKey="Abd El Aziz, M M" uniqKey="Abd El Aziz M">M.M. Abd El-Aziz</name></author><author><name sortKey="El Ashry, M F" uniqKey="El Ashry M">M.F. El-Ashry</name></author><author><name sortKey="Abu Safieh, L" uniqKey="Abu Safieh L">L. Abu-Safieh</name></author><author><name sortKey="Bhattacharya, S S" uniqKey="Bhattacharya S">S.S. Bhattacharya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bagnard, D" uniqKey="Bagnard D">D. Bagnard</name></author><author><name sortKey="Thomasset, N" uniqKey="Thomasset N">N. Thomasset</name></author><author><name sortKey="Lohrum, M" uniqKey="Lohrum M">M. Lohrum</name></author><author><name sortKey="Puschel, A W" uniqKey="Puschel A">A.W. Püschel</name></author><author><name sortKey="Bolz, J" uniqKey="Bolz J">J. Bolz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, A" uniqKey="Sharma A">A. Sharma</name></author><author><name sortKey="Levaillant, C J" uniqKey="Levaillant C">C.J. LeVaillant</name></author><author><name sortKey="Plant, G W" uniqKey="Plant G">G.W. Plant</name></author><author><name sortKey="Harvey, A R" uniqKey="Harvey A">A.R. Harvey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steup, A" uniqKey="Steup A">A. Steup</name></author><author><name sortKey="Lohrum, M" uniqKey="Lohrum M">M. Lohrum</name></author><author><name sortKey="Hamscho, N" uniqKey="Hamscho N">N. Hamscho</name></author><author><name sortKey="Savaskan, N E" uniqKey="Savaskan N">N.E. Savaskan</name></author><author><name sortKey="Ninnemann, O" uniqKey="Ninnemann O">O. Ninnemann</name></author><author><name sortKey="Nitsch, R" uniqKey="Nitsch R">R. Nitsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dutar, P" uniqKey="Dutar P">P. Dutar</name></author><author><name sortKey="Bassant, M H" uniqKey="Bassant M">M.H. Bassant</name></author><author><name sortKey="Senut, M C" uniqKey="Senut M">M.C. Senut</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richiardi, J" uniqKey="Richiardi J">J. Richiardi</name></author><author><name sortKey="Altmann, A" uniqKey="Altmann A">A. Altmann</name></author><author><name sortKey="Milazzo, A C" uniqKey="Milazzo A">A.C. Milazzo</name></author><author><name sortKey="Chang, C" uniqKey="Chang C">C. Chang</name></author><author><name sortKey="Chakravarty, M M" uniqKey="Chakravarty M">M.M. Chakravarty</name></author><author><name sortKey="Banaschewski, T" uniqKey="Banaschewski T">T. Banaschewski</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Alzheimers Dement</journal-id><journal-id journal-id-type="iso-abbrev">Alzheimers Dement</journal-id><journal-title-group><journal-title>Alzheimer's & Dementia</journal-title></journal-title-group><issn pub-type="ppub">1552-5260</issn><issn pub-type="epub">1552-5279</issn><publisher><publisher-name>Elsevier, Inc</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26993346</article-id><article-id pub-id-type="pmc">4982482</article-id><article-id pub-id-type="publisher-id">S1552-5260(16)00077-7</article-id><article-id pub-id-type="doi">10.1016/j.jalz.2016.01.010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Featured Article</subject></subj-group></article-categories><title-group><article-title>Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Schott</surname><given-names>Jonathan M.</given-names></name><email>j.schott@ucl.ac.uk</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author"><name><surname>Crutch</surname><given-names>Sebastian J.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Carrasquillo</surname><given-names>Minerva M.</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Uphill</surname><given-names>James</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>Shakespeare</surname><given-names>Tim J.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Ryan</surname><given-names>Natalie S.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Yong</surname><given-names>Keir X.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Lehmann</surname><given-names>Manja</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Ertekin-Taner</surname><given-names>Nilufer</given-names></name><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Graff-Radford</surname><given-names>Neill R.</given-names></name><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Boeve</surname><given-names>Bradley F.</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Murray</surname><given-names>Melissa E.</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Khan</surname><given-names>Qurat ul Ain</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Petersen</surname><given-names>Ronald C.</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Dickson</surname><given-names>Dennis W.</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Knopman</surname><given-names>David S.</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Rabinovici</surname><given-names>Gil D.</given-names></name><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>Bruce L.</given-names></name><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>González</surname><given-names>Aida Suárez</given-names></name><xref rid="aff1" ref-type="aff">a</xref><xref rid="aff7" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Gil-Néciga</surname><given-names>Eulogio</given-names></name><xref rid="aff7" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Snowden</surname><given-names>Julie S.</given-names></name><xref rid="aff8" ref-type="aff">h</xref></contrib><contrib contrib-type="author"><name><surname>Harris</surname><given-names>Jenny</given-names></name><xref rid="aff8" ref-type="aff">h</xref></contrib><contrib contrib-type="author"><name><surname>Pickering-Brown</surname><given-names>Stuart M.</given-names></name><xref rid="aff8" ref-type="aff">h</xref></contrib><contrib contrib-type="author"><name><surname>Louwersheimer</surname><given-names>Eva</given-names></name><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>van der Flier</surname><given-names>Wiesje M.</given-names></name><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Scheltens</surname><given-names>Philip</given-names></name><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Pijnenburg</surname><given-names>Yolande A.</given-names></name><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Galasko</surname><given-names>Douglas</given-names></name><xref rid="aff10" ref-type="aff">j</xref><xref rid="aff11" ref-type="aff">k</xref></contrib><contrib contrib-type="author"><name><surname>Sarazin</surname><given-names>Marie</given-names></name><xref rid="aff12" ref-type="aff">l</xref></contrib><contrib contrib-type="author"><name><surname>Dubois</surname><given-names>Bruno</given-names></name><xref rid="aff13" ref-type="aff">m</xref></contrib><contrib contrib-type="author"><name><surname>Magnin</surname><given-names>Eloi</given-names></name><xref rid="aff14" ref-type="aff">n</xref></contrib><contrib contrib-type="author"><name><surname>Galimberti</surname><given-names>Daniela</given-names></name><xref rid="aff15" ref-type="aff">o</xref></contrib><contrib contrib-type="author"><name><surname>Scarpini</surname><given-names>Elio</given-names></name><xref rid="aff15" ref-type="aff">o</xref></contrib><contrib contrib-type="author"><name><surname>Cappa</surname><given-names>Stefano F.</given-names></name><xref rid="aff16" ref-type="aff">p</xref></contrib><contrib contrib-type="author"><name><surname>Hodges</surname><given-names>John R.</given-names></name><xref rid="aff17" ref-type="aff">q</xref></contrib><contrib contrib-type="author"><name><surname>Halliday</surname><given-names>Glenda M.</given-names></name><xref rid="aff17" ref-type="aff">q</xref></contrib><contrib contrib-type="author"><name><surname>Bartley</surname><given-names>Lauren</given-names></name><xref rid="aff17" ref-type="aff">q</xref></contrib><contrib contrib-type="author"><name><surname>Carrillo</surname><given-names>Maria C.</given-names></name><xref rid="aff18" ref-type="aff">r</xref></contrib><contrib contrib-type="author"><name><surname>Bras</surname><given-names>Jose T.</given-names></name><xref rid="aff19" ref-type="aff">s</xref></contrib><contrib contrib-type="author"><name><surname>Hardy</surname><given-names>John</given-names></name><xref rid="aff19" ref-type="aff">s</xref></contrib><contrib contrib-type="author"><name><surname>Rossor</surname><given-names>Martin N.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Collinge</surname><given-names>John</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>Fox</surname><given-names>Nick C.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Mead</surname><given-names>Simon</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK</aff><aff id="aff2"><label>b</label>Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA</aff><aff id="aff3"><label>c</label>Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK</aff><aff id="aff4"><label>d</label>Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</aff><aff id="aff5"><label>e</label>Department of Neurology, Mayo Clinic, Rochester, MN, USA</aff><aff id="aff6"><label>f</label>UCSF, San Francisco, CA, USA</aff><aff id="aff7"><label>g</label>Memory Disorders Unit, Department of Neurology, University Hospital Virgen del Rocio, Seville, Spain</aff><aff id="aff8"><label>h</label>Institute of Brain, Behaviour and Mental Health, University of Manchester, UK</aff><aff id="aff9"><label>i</label>Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus, Amsterdam, Netherlands</aff><aff id="aff10"><label>j</label>Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands</aff><aff id="aff11"><label>k</label>UC San Diego/VA San Diego Healthcare System, San Diego, CA, USA</aff><aff id="aff12"><label>l</label>INSERM U610, Hôpital de la Salpêtrière, Paris, France</aff><aff id="aff13"><label>m</label>Centre des Maladies Cognitives et Comportementales, IM2A, ICM, Paris 6 University, France</aff><aff id="aff14"><label>n</label>Regional Memory Centre (CMRR), CHU Besançon, Besançon, France</aff><aff id="aff15"><label>o</label>University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Italy</aff><aff id="aff16"><label>p</label>Vita-Salute San Raffaele University, Milan, Italy</aff><aff id="aff17"><label>q</label>University of New South Wales, Sydney, Australia</aff><aff id="aff18"><label>r</label>Alzheimer's Association, Chicago, IL, USA</aff><aff id="aff19"><label>s</label>Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Tel.: +44 20 3448 3553; Fax: +44 20 3448 3104. <email>j.schott@ucl.ac.uk</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>1</day><month>8</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>8</month><year>2016</year></pub-date><volume>12</volume><issue>8</issue><fpage>862</fpage><lpage>871</lpage><permissions><copyright-statement>© 2016 The Authors</copyright-statement><copyright-year>2016</copyright-year><license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p></license></permissions><abstract id="abs0010"><sec><title>Introduction</title><p>The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain.</p></sec><sec><title>Methods</title><p>We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study.</p></sec><sec><title>Results</title><p>We confirm that variation in/near <italic>APOE/TOMM40</italic> (<italic>P</italic> = 6 × 10<sup>−14</sup>) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, <italic>P</italic> = .0007). We found evidence for risk in/near <italic>CR1</italic> (<italic>P</italic> = 7 × 10<sup>−4</sup>), <italic>ABCA7</italic> (<italic>P</italic> = .02) and <italic>BIN1</italic> (<italic>P</italic> = .04). ORs at variants near <italic>INPP5D</italic> and <italic>NME8</italic> did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed <italic>APOE</italic> and identified three novel loci: rs76854344 near <italic>CNTNAP5</italic> (<italic>P</italic> = 8 × 10<sup>−10</sup> OR = 1.9 [1.5–2.3]); rs72907046 near <italic>FAM46A</italic> (<italic>P</italic> = 1 × 10<sup>−9</sup> OR = 3.2 [2.1–4.9]); and rs2525776 near <italic>SEMA3C</italic> (<italic>P</italic> = 1 × 10<sup>−8</sup>, OR = 3.3 [2.1–5.1]).</p></sec><sec><title>Discussion</title><p>We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD.</p></sec></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>Posterior cortical atrophy</kwd><kwd>Alzheimer's disease</kwd><kwd>Genetics</kwd><kwd>GWAS</kwd><kwd>Selective vulnerability</kwd><kwd><italic>APOE</italic></kwd></kwd-group></article-meta></front><body><sec id="sec1"><label>1</label><title>Introduction</title><p>Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome, typically a variant of Alzheimer's disease (AD), although occasionally due to other pathologies including dementia with Lewy bodies, corticobasal degeneration, and prion disease <xref rid="bib1" ref-type="bibr">[1]</xref>. Patients with PCA present with combinations of cognitive problems attributable to posterior cortical dysfunction and in particular difficulties with higher level visual processing including simultanagnosia, optic apraxia, optic ataxia, and visual disorientation; other features may include dyslexia, dyscalculia, dysgraphia, and limb dyspraxia. In contrast with typical, amnestic AD, memory is relatively spared until the disease becomes advanced. MR brain imaging in PCA typically shows parieto-occipital lobe atrophy with relative preservation of medial temporal lobe structures <xref rid="bib2" ref-type="bibr">[2]</xref>; fluoro-deoxyglucose positron emission tomography (PET) shows prominent posterior cortical hypometabolism <xref rid="bib3" ref-type="bibr">[3]</xref>; and in a single case study using the AV1451 tau PET tracer, posterior cortical tau deposition <xref rid="bib4" ref-type="bibr">[4]</xref>. By contrast, PET imaging using amyloid-binding ligands typically shows global amyloid deposition <xref rid="bib3" ref-type="bibr">[3]</xref>. Aside from the imaging and cognitive differences, patients with PCA are typically younger than those with typical amnestic late-onset AD, usually with disease onset in the sixth or seventh decade <xref rid="bib1" ref-type="bibr">[1]</xref>. PCA is almost invariably a sporadic disorder, and the risk factors for developing the syndrome are unknown. Understanding the genetic architecture of the PCA variant of AD may provide insights both into factors predisposing to young onset AD, as well as mechanisms underlying regional vulnerability in AD.</p><p>To date, only a few, single-center studies have addressed genetic risk for PCA <xref rid="bib5" ref-type="bibr">[5]</xref>, <xref rid="bib6" ref-type="bibr">[6]</xref>, <xref rid="bib7" ref-type="bibr">[7]</xref>, <xref rid="bib8" ref-type="bibr">[8]</xref>, <xref rid="bib9" ref-type="bibr">[9]</xref>, <xref rid="bib10" ref-type="bibr">[10]</xref>, and due to the rarity of the syndrome all have been relatively small, the largest being a maximum of 81 cases <xref rid="bib9" ref-type="bibr">[9]</xref>. Some, but not all, of these studies have suggested that despite their early-disease onset, patients with PCA may be less likely than expected to have an <italic>APOE</italic> ε4 allele, the commonest risk factor for late-onset AD. Other studies have suggested that there may be differences in some of the more recently identified genetic risks for AD in patients with PCA <xref rid="bib9" ref-type="bibr">[9]</xref>. Recognizing the rarity of this AD variant, we formed an international consortium comprising eleven centers, using clinical diagnostic criteria to define cases of PCA, with the principal aim of determining whether <italic>APOE</italic> ε4 and genetic risks from recent genome-wide association studies (GWAS) of AD and dementia with Lewy bodies (DLB, see below) are risk factors for the PCA variant of AD. In a second, exploratory analysis, we performed a pilot GWAS analysis to identify novel putative genetic risk factors for PCA.</p></sec><sec id="sec2"><label>2</label><title>Methods</title><sec id="sec2.1"><label>2.1</label><title>PCA patients and controls</title><p>After an inaugural multidisciplinary meeting of PCA researchers <xref rid="bib11" ref-type="bibr">[11]</xref>, latterly formalized as the Alzheimer's Association's International Society to Advance Alzheimer's Research and Treatment (ISTAART) Professional Interest Area in Atypical AD and Associated Syndromes, an international collaborative group was established to assess genetic risk factors for PCA. Researchers identified individuals with PCA, in whom a deoxyribo nucleic acid (DNA) sample was available. Patients who the referring physician had diagnosed with AD, had multidomain cognitive impairment fulfilling criteria for AD dementia, and had one or both of two published criteria for PCA, as proposed by Tang-Wai <xref rid="bib5" ref-type="bibr">[5]</xref> and Mendez <xref rid="bib12" ref-type="bibr">[12]</xref> (<xref rid="tbl1" ref-type="table">Table 1</xref>) were included. Additional data collected included gender, age at disease onset, age at death (where applicable), and whether there was molecular (cerebrospinal fluid or amyloid PET using locally defined ranges) evidence or pathologic confirmation of underlying AD pathology. Each site had appropriate local ethical approvals in place, and all participants gave informed written consent. Controls were from UK, USA, and Germany (see below).</p></sec><sec id="sec2.2"><label>2.2</label><title>Genetic and statistical analyses</title><p>DNA samples were analyzed at the MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, UCL. PCA samples were genotyped on Illumina 660 arrays (n = 54, UCL cohort only) and OmniExpress arrays (n = 239, all cohorts); in total, 293 passed sample quality control, implemented using PLINK. Controls were genotyped on Illumina 550 (n = 809, KORA F4 German, PMID: <ext-link ext-link-type="uri" xlink:href="pmid:16032514" id="intref0010">16032514</ext-link>), OmniExpress (n = 1185, Geisinger US <ext-link ext-link-type="uri" xlink:href="http://www.geisinger.org" id="intref0015">http://www.geisinger.org</ext-link>), Illumina 2.5 M (n = 1882, KORA F3 German), Illumina 5M (n = 1651, Framingham US, see acknowledgments), and Illumina 1.2 M (n = 5020, WTCCC2 UK, see acknowledgments) arrays. Physical locations refer to the Feb 2009 (GRCh37/hg19) assembly. We excluded SNPs with a minor allele frequency (MAF) < 1% (n = 70,042 from OmniExpress case arrays); genotyping rate <99% (n = 85,086 from OmniExpress case arrays); or Hardy-Weinberg Equilibrium (HWE) exact test <italic>P</italic> < 10<sup>−3</sup> in controls. Cases with call rate <98% (n = 6) as well as ethnic outliers (n = 2) were excluded after visualization of multidimensional scaling plots. Related and duplicate cases were removed by IBS/IBD calculation (n = 1) and re-examination of patient data, as they became available post genotyping (n = 2). A Pi-Hat (proportion identity by descent) threshold of >0.1875 was used, which should exclude first and second degree relatives. Two duplicates removed due to later availability of patient data were also included within the six cases removed for low call rate thus bringing the total number of cases removed to nine. Owing to the multitude of different genotyping platforms, control comparisons were carried out sequentially and exclusions removed at each stage. A total of 840 KORAF4 German controls were originally genotyped; 17 with call rate <98%, six with Pi-Hat > 0.1875 and eight MDS outliers were removed. A total of 1950 KORAF3 German controls were originally downloaded; three with call rate <98%, 57 with Pi-Hat > 0.1875, and eight MDS outliers were removed. A total of 1264 Geisinger US controls were originally downloaded; two with call rate <98%, 69 with Pi-Hat >0.1875, and eight MDS outliers were removed. 2467 FHS US controls were originally downloaded; 16 with call rate <98%, 793 with Pi-Hat >0.1875 and seven MDS outliers were removed. 5050 WTCCC2 UK controls were generated from available raw IDAT files; 26 with call rate <98%, four with Pi-Hat > 0.1875, and zero MDS outliers were removed (see <xref rid="appsec1" ref-type="sec">Supplementary Table 1</xref>). All remaining cases and controls were finally visualized on an MDS plot (see <xref rid="appsec1" ref-type="sec">Supplementary Fig. 1</xref>), outlier detection was performed using PLINK v1.07, and no further outliers were detected. IBS/IBD estimation of the final cases and controls also lead to no further exclusions based on relatedness. Shapeitv2 was used, in conjunction with the 1000 Genomes Phase 1 Integrated variant set (b37 March 2012 release), to align all data relative to the positive strand <xref rid="bib13" ref-type="bibr">[13]</xref>. To avoid potential downstream cross platform confusion, however, we removed any A/T or G/C transversions to phase each chromosome from each platform separately before imputation using Impute2 (v2.3.0). GTOOL (v0.6.6) was used to extract and collate samples into their respective cohorts for association testing <xref rid="bib14" ref-type="bibr">[14]</xref>. Association testing was performed using SNPtest_v2.5-beta4 employing the frequentist (additive model) score method which involves weighting by the likelihood of each imputed genotype <xref rid="bib15" ref-type="bibr">[15]</xref>. Four population covariates derived from IBS/IBD analysis in PLINK were used in the association analysis <xref rid="bib16" ref-type="bibr">[16]</xref>, <xref rid="bib17" ref-type="bibr">[17]</xref>. The case-control association test statistic inflation factor was 1.06 (<xref rid="appsec1" ref-type="sec">Supplementary Fig. 2</xref>). Any association statistics mentioned in the results section are shown with standard genomic control (<italic>P</italic><sub><italic>GC</italic></sub>) corrected and uncorrected <italic>P</italic> values. Post association-testing QC excluded markers with a MAF <1% and departure from HWE, in both combined and any single control cohort <italic>P</italic> < 10<sup>−4</sup>. We also excluded markers with a SNPtestv2 derived “info metric” and “add info metric” below 0.9. The final autosomal analysis thus included 5.9 M markers.</p><p>We assessed whether the genetic risks for typical AD and PCA were different by comparing odds ratios (OR) between our study and those published in typical AD <xref rid="bib18" ref-type="bibr">[18]</xref>. We employed a Wald-type test, first calculating the standard error of the difference in log (OR) from the reported CIs. We then divided the empirical difference in log (OR) by its standard error, and thus derived a z-score and <italic>P</italic> value, relying on the approximate normality of log (OR) estimates from large samples. In the main analysis of candidate SNPs, we used a Bonferroni corrected association threshold of <italic>P</italic> < .002 based on the testing of a lead SNP from 24 independent loci derived from studies of AD <xref rid="bib18" ref-type="bibr">[18]</xref> and DLB <xref rid="bib19" ref-type="bibr">[19]</xref>.</p><p>Although the typical samples sizes that are required to discover novel genome-wide significant risk factors in complex disorders are in the thousands, there are some precedents of strong genetic effects detected with small but phenotypically homogenous samples, including variants at <italic>APOE</italic> in AD <xref rid="bib20" ref-type="bibr">[20]</xref>, <italic>PRNP</italic> in prion disease <xref rid="bib21" ref-type="bibr">[21]</xref>, and complement factor H in age related macular degeneration <xref rid="bib22" ref-type="bibr">[22]</xref>. We therefore performed an exploratory genome-wide association study using established methodologies that account for population structure and with imputation of SNPs not present on the genotyping arrays. As PCA is a clinical syndrome that may be due to pathologies other than AD, we also assessed the odds ratios at SNPs of interest in a subset of patients with biomarker/pathological evidence for AD.</p></sec></sec><sec id="sec3"><label>3</label><title>Results</title><sec id="sec3.1"><label>3.1</label><title>Patients and demographics</title><p>A total of 302 samples fulfilling entry criteria to the study were available from eleven centers: University College London (n = 94); Mayo Clinic, USA (n = 77); University of California San Francisco, USA (n = 25); University of Seville, Spain (n = 25); University of Manchester, UK (n = 20); VU University, Netherlands (n = 17); University of California San Diego, USA (n = 16); INSERM, France (n = 10); University of Milan, Italy (n = 6); CHU Besançon, France (n = 6); and University of New South Wales, Australia (n = 6). Demographics are shown in <xref rid="tbl2" ref-type="table">Table 2</xref>. All samples fulfilled Tang-Wai clinical criteria for PCA <xref rid="bib5" ref-type="bibr">[5]</xref>, and in the 225 samples for which data were available, 97.3% also fulfilled Mendez criteria <xref rid="bib12" ref-type="bibr">[12]</xref>; 41% of the cohort was male. Mean (±SD) age at symptom onset was 58.9 ± 6.9 years, and 82.5% had young onset dementia, as defined by age at onset of <65 years. Thirty-four patients had died, with a mean age at death of 68.0 (±7.7) years. Molecular or pathologic evidence for underlying Alzheimer pathology was available for 82 (27%), of whom 52 had a CSF profile compatible with AD; 32 had a positive amyloid PET scan; and 15 had autopsy proven AD. None had evidence for pathology or biomarkers for non-AD pathology.</p><p>DNA from nine individuals failed array quality control, and statistical analyses were done on the remaining 293/302 samples (see <xref rid="tbl2" ref-type="table">Table 2</xref>). We also considered the associations in the sub-sample of 82 with biomarker/autopsy evidence for underlying AD pathology.</p></sec><sec id="sec3.2"><label>3.2</label><title>Comparisons at known genetic loci for AD and DLB</title><p>Results of the genetic analysis of candidate risk factors for the whole PCA cohort are shown in <xref rid="tbl2" ref-type="table">Table 2</xref>. First, we considered 24 SNPs known to be genetic risk factors in AD and/or DLB. The best proxy genotyped for the <italic>APOE</italic> ε4 AD-risk allele, rs2075650, located on chromosome 19 in the <italic>TOMM40</italic> gene and 13kb upstream of <italic>APOE</italic>, was identified as a strong risk factor for PCA (OR 2.03, [95% CI = 1.68–2.46], <italic>P</italic> = 6 × 10<sup>−14</sup>, <italic>P</italic><sub>GC</sub> = 3 × 10<sup>−13</sup>; <xref rid="fig1" ref-type="fig">Fig. 1</xref> and <xref rid="fig2" ref-type="fig">Fig. 2</xref>A). rs3818361 located on chromosome 1 in <italic>CR1</italic> was also significantly associated (ORs = 1.38 [1.14–1.67], <italic>P</italic> = 7 × 10<sup>−4</sup>, <italic>P</italic><sub>GC</sub> = 1 × 10<sup>−3</sup>; <xref rid="fig2" ref-type="fig">Fig. 2</xref>B). rs3764650 in <italic>ABCA7</italic> (OR = 1.39 [1.07–1.8], <italic>P</italic> = .02, <italic>P</italic><sub>GC</sub> = .02) and rs744373 upstream of <italic>BIN1</italic> (OR = 1.2 [1.01–1.43], <italic>P</italic> = .04, <italic>P</italic><sub>GC</sub> = .05) reached nominal significance but did not surpass our Bonferroni corrected threshold of <italic>P</italic> < .002. Other candidate SNPs showed no evidence of association.</p><p>In the subset of individuals with either biomarker (CSF or amyloid PET) or pathologic evidence for underlying AD (n = 82), rs2075650 (at the <italic>APOE/TOMM40</italic> locus, subsequently referred to as <italic>APOE</italic>) was again identified as a risk factor with a similar OR to the whole group (OR = 2.00 [1.39–2.89] <italic>P</italic> = 9 × 10<sup>−5</sup>, <italic>P</italic><sub>GC</sub> = 1 × 10<sup>−4</sup>). rs3818361 (<italic>CR1</italic>) and rs3764650 (<italic>ABCA7</italic>) both showed nominally significant differences compared with controls (<italic>CR1</italic> OR = 1.7 [1.20–2.41], <italic>P</italic> = .003, <italic>P</italic><sub>GC</sub> = .004; <italic>ABCA7</italic> OR = 1.83 [1.17–2.86], <italic>P</italic> = .009, <italic>P</italic><sub>GC</sub> = .01). There was no evidence for an effect of <italic>BIN1</italic> (OR = 1.08 [0.76–1.52], <italic>P</italic> = .65) in the biomarker cohort.</p></sec><sec id="sec3.3"><label>3.3</label><title>Comparing risk for PCA to typical AD</title><p>Comparing odds ratios and the nominal risk conferred in the whole PCA cohort against the most recently published mega-meta studies of typical AD <xref rid="bib16" ref-type="bibr">[16]</xref>, the effect size seen at the <italic>APOE</italic> locus was significantly less strong in PCA than for typical AD (PCA: OR 2.03, typical AD: OR 2.83, <italic>P</italic> = .0007, <italic>P</italic><sub>GC</sub> = .001, see methods). Although there was no evidence for risk in PCA vs controls, the risk effects at rs35349669 in <italic>INPP5D</italic> (<italic>P</italic> = .02, <italic>P</italic><sub>GC</sub> = .02) and rs2718058 upstream of <italic>NME8</italic> (<italic>P</italic> = .03, <italic>P</italic><sub>GC</sub> = .04) both were nominally different in PCA than typical AD.</p></sec><sec id="sec3.4"><label>3.4</label><title>Exploratory GWAS</title><p>As several different array platforms were used in the study, only 210,670 SNPs were genotyped across all samples. In this set, there was little evidence of inflation in the association test statistic (λ = 1.05). Only the proxy for the <italic>APOE</italic> ε4 AD-risk allele, rs2075650, achieved genome-wide significance. We went on to analyze 5.9-M SNPs in the imputed data set. Aside from chromosome 19 (<italic>APOE</italic> locus), three loci on chromosomes 7, 2, and 6 respectively were of interest (<xref rid="fig1" ref-type="fig">Fig. 1</xref>). rs2525776 on chromosome 7, upstream of <italic>SEMA3C</italic> (OR 3.3 [2.1–5.1], <italic>P</italic> = 1.4 × 10<sup>−8</sup>, <italic>P</italic><sub>GC</sub> = 4 × 10<sup>−8</sup>; <xref rid="fig2" ref-type="fig">Fig. 2</xref>C); rs76854344 on chromosome 2, upstream of <italic>CNTNAP5</italic>, (OR 1.9 [1.5–2.3], <italic>P</italic> = 8.0 × 10<sup>−10</sup>, <italic>P</italic><sub>GC</sub> = 2 × 10<sup>−9</sup>; <xref rid="fig2" ref-type="fig">Fig. 2</xref>D), and rs72907046 on chromosome 6, downstream of <italic>FAM46A</italic> (OR 3.2 [2.1–4.9], <italic>P</italic> = 1.1 × 10<sup>−9</sup>, <italic>P</italic><sub>GC</sub> = 3 × 10<sup>−9</sup>; <xref rid="fig2" ref-type="fig">Fig. 2</xref>E) were all associated with PCA. Restricting the analysis to the 82 individuals with biomarker/pathology evidence for underlying AD pathology, the corresponding odds ratios were similar: 3.8 [1.8–8.2], <italic>P</italic> = 2.8 × 10<sup>−4</sup> for rs2525776; 1.8 [1.2–2.7], <italic>P</italic> = 2.1 × 10<sup>−3</sup> for rs76854344; and 2.5 [1.0–6.1], <italic>P</italic> = 2.7 × 10<sup>−2</sup> for rs72907046. None of these three loci showed any evidence of association with typical AD on the IGAP AD-risk GWAS meta-analysis. A full list of suggestive associations <italic>P</italic> < 10<sup>−4</sup> based on the SNPs represented on case and control arrays (the intersection SNPs) is available in a <xref rid="appsec1" ref-type="sec">Supplementary Table 2</xref>, and summary statistics from the entire data set is available at the NHGRI-EBI GWAS Catalog.</p></sec></sec><sec id="sec4"><label>4</label><title>Discussion</title><p>We report findings from a consortium to study genetic risk factors in PCA, a rare predominantly early-onset cognitive disorder characterized by progressive and disproportionately posterior cortical dysfunction and atrophy, and usually associated with AD-type pathology. Our primary aim was to explore the relationship between PCA and a predetermined list of candidate SNPs derived from studies of typical AD and DLB. Our main findings are the identification of genetic risk for PCA at some of the known AD-risk loci, but not at the two DLB-risk loci that were tested (<xref rid="tbl3" ref-type="table">Table 3</xref>). We demonstrate PCA-risk association with variants in or near <italic>APOE, CR1, ABCA7</italic> and <italic>BIN1</italic> in the whole cohort, but only those at <italic>APOE</italic>, <italic>CR1</italic>, and <italic>ABCA7</italic> remain nominally significant in the small molecularly defined subgroup. We also show evidence for nonoverlapping CIs of genetic risk at <italic>APOE, INPP5D</italic>, and <italic>NME8</italic>. Although this is by far the largest study of PCA to date, our relatively small sample size remains underpowered to detect genome-wide significant associations at risk loci with small effect sizes, such as those shown to associate in AD-risk GWAS. However, our exploratory GWAS nominates the three novel loci, <italic>SEMA3C</italic>, <italic>CNTNAP5</italic>, and <italic>FAM46A</italic>, which achieved genome-wide significance, as potential genes of interest in PCA.</p><p>Although still small for genetic studies, this collection is the result of a global collaborative effort and is considerably larger than any previous studies of PCA reporting varying evidence that <italic>APOE</italic> is a risk factor <xref rid="bib5" ref-type="bibr">[5]</xref>, <xref rid="bib6" ref-type="bibr">[6]</xref>, <xref rid="bib7" ref-type="bibr">[7]</xref>, <xref rid="bib8" ref-type="bibr">[8]</xref>, <xref rid="bib9" ref-type="bibr">[9]</xref>, <xref rid="bib10" ref-type="bibr">[10]</xref>. Although the vast majority of samples in previous studies overlap with the present study, individual studies comprise <∼25% of the current total. We found robust genetic association at <italic>APOE</italic> but with an odds ratio significantly smaller than those seen in typical AD. <italic>APOE</italic> is the best established and strongest risk factor for sporadic AD and has been associated not only with increased risk <italic>per se</italic>, but also with earlier disease onset <xref rid="bib23" ref-type="bibr">[23]</xref>, the rate of hippocampal atrophy <xref rid="bib24" ref-type="bibr">[24]</xref> and more memory led disease. However, the situation is more complex in early-onset AD which is associated both with a greater proportion of nonamnestic presentations, and perhaps a relatively reduced proportion of <italic>APOE</italic> ε4 carriers <xref rid="bib25" ref-type="bibr">[25]</xref>. Studies investigating <italic>APOE</italic> risk for PCA (or as it was sometimes previously defined, biparietal AD <xref rid="bib6" ref-type="bibr">[6]</xref>), have shown mixed results, perhaps due to differences in case definition, and the limited sample size of each study. In this study of PCA, by far the largest yet published, we confirm that <italic>APOE</italic> is a risk factor for PCA, but that it is a weaker risk factor than for typical AD.</p><p>Addressing risk factors other than <italic>APOE</italic>, the largest single previous study—which included samples also used in this analysis—found nominally significant association with SNPs in or near <italic>CLU</italic>, <italic>BIN1</italic>, and <italic>ABCA7</italic><xref rid="bib9" ref-type="bibr">[9]</xref>. We found evidence of association in the same direction for the SNP at <italic>ABCA7</italic> both in the whole cohort and those with biomarker evidence for AD; for <italic>BIN1</italic> in the whole cohort alone; but could not confirm that SNPs near to <italic>CLU</italic> are risk factors. Aside from <italic>APOE</italic>, only variants in <italic>CR1</italic> surpassed our statistical threshold for multiple testing in the whole cohort; these variants also showed nominal significance in the biomarker positive subgroup. Estimates of effect size were greater in PCA than those in typical AD at each associated locus aside from <italic>APOE</italic>. Although these differences were only nominally statistically significant, the four risk loci we report are among the strongest known common genetic risk factors for typical AD (<xref rid="tbl3" ref-type="table">Table 3</xref>). <italic>CR1</italic> has multiple functions including the regulation of complement and phagocytosis of immune complexes and pathogens, which are increasingly though to be relevant to AD pathogenesis <xref rid="bib26" ref-type="bibr">[26]</xref>. <italic>ABCA7</italic> may play a role in AD through regulation of phagocytosis or lipid metabolism. <italic>BIN1</italic> mechanisms in AD are unclear but may be involved in endocytosis and the recycling of endocytic vesicles <xref rid="bib27" ref-type="bibr">[27]</xref>.</p><p>Although they did not confer significant alteration of PCA risk, we found that odds ratio confidence intervals for SNPs at or near to <italic>INPP5D</italic> and <italic>NME8</italic> in PCA did not overlap those of typical AD and showed directionally opposite effects, <italic>INPP5D</italic> was identified as a risk factor for AD in a recent large meta-analysis and plays an important role in a number of inflammatory processes. There is little evidence for the function of <italic>NME8</italic> in the central nervous system, although a role in modification of oxidative stress has been proposed <xref rid="bib28" ref-type="bibr">[28]</xref>. Although these findings were only nominally significant and need independent replication, they do raise the possibility that syndromic variants of AD may be differentially associated with alterations in certain risk genes, perhaps through altered responses to inflammation or stress.</p><p>The results of our exploratory genome-wide study implicate three potential strong risk loci, near to <italic>CNTNAP5</italic>, <italic>FAM46A</italic>, and upstream of <italic>SEMA3C</italic>. The regions of strong LD with these associations did not include directly genotyped SNPs across all platforms, and therefore false-positive associations related to differential accuracy of imputation between case and control arm of the study remain possible. With the caveat that these findings must therefore be considered preliminary and require follow-up replication in an independent sample and by direct genotyping, it is notable that all three genes have roles in processes potentially relevant to PCA. Contactin-associated protein-like 5 gene (<italic>CNTNAP5</italic>) belongs to a subgroup of the neurexin family of multidomain transmembrane proteins involved in cell adhesion and intercellular communication in the central nervous system and has been implicated as a risk factor for bipolar disorder and autism spectrum disorders <xref rid="bib29" ref-type="bibr">[29]</xref>. Family with sequence similarity 46, member A1 (<italic>FAM46A</italic>), originally <italic>C6orf37</italic>, is preferentially expressed within the neural retina <xref rid="bib30" ref-type="bibr">[30]</xref> and has been implicated in cell signaling pathways related to retinal neurodegeneration <xref rid="bib31" ref-type="bibr">[31]</xref>. Class III semaphorins including Semaphorin 3C (<italic>SEMA3C</italic>) have been examined as potential modifying factors in neurodegeneration through interactions with plexins and neuropilins. <italic>SEMA3C</italic> has been identified as a chemotrophic molecule influencing attractive guidance for cortical axon development <xref rid="bib32" ref-type="bibr">[32]</xref>; the expression of <italic>SEMA3C</italic> and its receptors have been shown to influence the maturation of the visual system <xref rid="bib33" ref-type="bibr">[33]</xref>; and <italic>SEMA3C</italic> is also expressed in the hippocampus, where it has a role in influencing the afferent connections of the developing hippocampus and in particular the ingrowth of septo-hippocampal connections <xref rid="bib34" ref-type="bibr">[34]</xref>, the major cholinergic connections implicated in learning and memory <xref rid="bib35" ref-type="bibr">[35]</xref>. Finally, <italic>SEMA3C</italic> expression has been shown to correlate with functional network connectivity within the brain <xref rid="bib36" ref-type="bibr">[36]</xref>. Although at this stage speculative, it is possible therefore that perhaps subtle differences in cortical development might influence where pathology starts and/or how it spreads through the brain if a neurodegeneration process is initiated later in life. The fact that all three of these novel genetic risks showed nominal associations in the relatively small subset of individuals with biomarker evidence for AD and the absence of similar evidence of association in any of these genes with IGAP studies of typical AD suggest that if confirmed, these loci may be specific risks for PCA due to Alzheimer's disease.</p><p>The main limitation of our study is the necessarily modest sample size of this very rare disorder, noting that the case numbers presented here were only achievable through the establishment of an international consortium. We plan to continue to collect further samples to allow for replication in due course. Based on standard power calculations in case-control studies, even in the favorable situation of completely accurate imputation of the functional SNP we are only adequately powered to detect effect sizes of OR >1.5, for common candidate SNPs, and the only common genetic risk factor of this strength in typical AD is <italic>APOE</italic>. We made comparisons with studies of patients diagnosed with typical AD; however, these patients and/or studies are different in multiple ways including the genotyping platforms used, later age at clinical onset, potential pathologic heterogeneity, and most probably differences in geographical location, all of which could confound the comparison. Although PCA is underpinned by AD pathology in most cases, we only had evidence for underlying AD in a proportion (∼1/4), and we cannot confirm that the genetic risks we have determined are specific for the AD variant of PCA rather than the syndrome of PCA or for young onset AD. However, allowing for the fact that the confidence intervals are inevitably large, it is notable that the estimates for the odds ratios for <italic>APOE</italic>, <italic>CR1</italic>, and <italic>ABCA7</italic>, and the putative genes identified in our exploratory GWAS were similar or larger in the proportion with molecular evidence for AD, suggesting that the risk we identify are likely to be for the AD variant of PCA, rather than for the syndrome per se.</p><p>One of the major outstanding issues in neurodegenerative disease research is an explanation for the often very striking phenotypic heterogeneity underpinned by the same broad core pathology. Possibilities for phenotype modification include demographic and environmental factors, including age at onset, or perhaps more likely complex gene and/or environment interactions and/or factors related to the misfolded proteins and their propagation, tissue or network selectivity and toxicity. The results of this study suggest that subtle differences in established risk factors may be associated with some of this heterogeneity and provide testable suggestions for novel genes that may influence the development of the hippocampal and visual system, which may influence the development of the PCA phenotype relative to other syndromes. If confirmed in future studies, next generation sequencing may be useful in determining whether these findings might be underpinned by rare variants with large effect sizes. More broadly, genetic investigation of well-phenotyped AD variants may provide important insights into disease biology in typical AD.<boxed-text id="dtbox1"><caption><title>Research in context</title></caption><p><list list-type="simple"><list-item id="o0010"><label>1.</label><p>Systematic review: Reviewing the literature for publications investigating the genetics of posterior cortical atrophy (PCA), there is conflicting evidence for the role of <italic>APOE</italic> in the PCA variant of Alzheimer's disease AD), and limited evidence for the more recently identified genetic risks for AD.</p></list-item><list-item id="o0015"><label>2.</label><p>Interpretation: Through the establishment of an international consortium to create the largest study exploring the genetics of PCA to date, we demonstrate that (1) <italic>APOE</italic> is a risk factor for PCA but confers a smaller risk than for typical AD; (2) some of the genetic risks for typical AD are also associated with PCA risk; and (3) nominate three novel risk loci for PCA.</p></list-item><list-item id="o0020"><label>3.</label><p>Future directions: These data provide clear directions and testable hypotheses for future studies, including (1) the establishment of a replication cohort and (2) investigation of the identified genes as factors influencing selective vulnerability in AD.</p></list-item></list></p></boxed-text></p></sec></body><back><ref-list><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Crutch</surname><given-names>S.J.</given-names></name><name><surname>Lehmann</surname><given-names>M.</given-names></name><name><surname>Schott</surname><given-names>J.M.</given-names></name><name><surname>Rabinovici</surname><given-names>G.D.</given-names></name><name><surname>Rossor</surname><given-names>M.N.</given-names></name><name><surname>Fox</surname><given-names>N.C.</given-names></name></person-group><article-title>Posterior cortical atrophy</article-title><source>Lancet Neurol</source><volume>11</volume><year>2012</year><fpage>170</fpage><lpage>178</lpage><pub-id pub-id-type="pmid">22265212</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="journal" id="sref2"><person-group person-group-type="author"><name><surname>Lehmann</surname><given-names>M.</given-names></name><name><surname>Koedam</surname><given-names>E.L.</given-names></name><name><surname>Barnes</surname><given-names>J.</given-names></name><name><surname>Bartlett</surname><given-names>J.W.</given-names></name><name><surname>Ryan</surname><given-names>N.S.</given-names></name><name><surname>Pijnenburg</surname><given-names>Y.A.L.</given-names></name></person-group><article-title>Posterior cerebral atrophy in the absence of medial temporal lobe atrophy in pathologically-confirmed Alzheimer's disease</article-title><source>Neurobiol Aging</source><volume>33</volume><year>2012</year><fpage>627</fpage><pub-id pub-id-type="pmid">21596458</pub-id></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal" id="sref3"><person-group person-group-type="author"><name><surname>Lehmann</surname><given-names>M.</given-names></name><name><surname>Ghosh</surname><given-names>P.M.</given-names></name><name><surname>Madison</surname><given-names>C.</given-names></name><name><surname>Laforce</surname><given-names>R.</given-names></name></person-group><article-title>Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease</article-title><source>Brain</source><volume>136</volume><year>2013</year><fpage>844</fpage><lpage>858</lpage><pub-id pub-id-type="pmid">23358601</pub-id></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal" id="sref4"><person-group person-group-type="author"><name><surname>Ossenkoppele</surname><given-names>R.</given-names></name><name><surname>Schonhaut</surname><given-names>D.R.</given-names></name><name><surname>Baker</surname><given-names>S.L.</given-names></name><name><surname>O'Neil</surname><given-names>J.P.</given-names></name><name><surname>Janabi</surname><given-names>M.</given-names></name><name><surname>Ghosh</surname><given-names>P.M.</given-names></name></person-group><article-title>Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy</article-title><source>Ann Neurol</source><volume>77</volume><year>2015</year><fpage>338</fpage><lpage>342</lpage><pub-id pub-id-type="pmid">25448043</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sref5"><person-group person-group-type="author"><name><surname>Tang-Wai</surname><given-names>D.F.</given-names></name><name><surname>Graff-Radford</surname><given-names>N.R.</given-names></name><name><surname>Boeve</surname><given-names>B.F.</given-names></name><name><surname>Dickson</surname><given-names>D.W.</given-names></name><name><surname>Parisi</surname><given-names>J.E.</given-names></name><name><surname>Crook</surname><given-names>R.</given-names></name></person-group><article-title>Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy</article-title><source>Neurology</source><volume>63</volume><year>2004</year><fpage>1168</fpage><lpage>1174</lpage><pub-id pub-id-type="pmid">15477533</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sref6"><person-group person-group-type="author"><name><surname>Schott</surname><given-names>J.M.</given-names></name><name><surname>Ridha</surname><given-names>B.H.</given-names></name><name><surname>Crutch</surname><given-names>S.J.</given-names></name><name><surname>Healy</surname><given-names>D.G.</given-names></name><name><surname>Uphill</surname><given-names>J.B.</given-names></name><name><surname>Warrington</surname><given-names>E.K.</given-names></name></person-group><article-title>Apolipoprotein e genotype modifies the phenotype of Alzheimer disease</article-title><source>Arch Neurol</source><volume>63</volume><year>2006</year><fpage>155</fpage><lpage>156</lpage><pub-id pub-id-type="pmid">16401755</pub-id></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="journal" id="sref7"><person-group person-group-type="author"><name><surname>van der Flier</surname><given-names>W.M.</given-names></name><name><surname>Schoonenboom</surname><given-names>S.N.</given-names></name><name><surname>Pijnenburg</surname><given-names>Y.A.</given-names></name><name><surname>Fox</surname><given-names>N.C.</given-names></name><name><surname>Scheltens</surname><given-names>P.</given-names></name></person-group><article-title>The effect of APOE genotype on clinical phenotype in Alzheimer disease</article-title><source>Neurology</source><volume>67</volume><year>2006</year><fpage>526</fpage><lpage>527</lpage><pub-id pub-id-type="pmid">16894123</pub-id></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal" id="sref8"><person-group person-group-type="author"><name><surname>Snowden</surname><given-names>J.S.</given-names></name><name><surname>Stopford</surname><given-names>C.L.</given-names></name><name><surname>Julien</surname><given-names>C.L.</given-names></name><name><surname>Thompson</surname><given-names>J.C.</given-names></name><name><surname>Davidson</surname><given-names>Y.</given-names></name><name><surname>Gibbons</surname><given-names>L.</given-names></name></person-group><article-title>Cognitive Phenotypes in Alzheimer's Disease and Genetic Risk</article-title><source>Cortex</source><volume>43</volume><year>2007</year><fpage>835</fpage><lpage>845</lpage><pub-id pub-id-type="pmid">17941342</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sref9"><person-group person-group-type="author"><name><surname>Carrasquillo</surname><given-names>M.M.</given-names></name><name><surname>Khan</surname><given-names>Q.U.</given-names></name><name><surname>Murray</surname><given-names>M.E.</given-names></name><name><surname>Krishnan</surname><given-names>S.</given-names></name><name><surname>Aakre</surname><given-names>J.</given-names></name><name><surname>Pankratz</surname><given-names>V.S.</given-names></name></person-group><article-title>Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD</article-title><source>Neurology</source><volume>82</volume><year>2014</year><fpage>1455</fpage><lpage>1462</lpage><pub-id pub-id-type="pmid">24670887</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal" id="sref10"><person-group person-group-type="author"><name><surname>Carrasquillo</surname><given-names>M.M.</given-names></name><name><surname>Barber</surname><given-names>I.</given-names></name><name><surname>Lincoln</surname><given-names>S.J.</given-names></name><name><surname>Murray</surname><given-names>M.E.</given-names></name><name><surname>Camsari</surname><given-names>G.B.</given-names></name><name><surname>Khan</surname><given-names>Q.U.</given-names></name></person-group><article-title>Evaluating pathogenic dementia variants in posterior cortical atrophy</article-title><source>Neurobiol Aging</source><volume>37</volume><year>2016</year><fpage>38</fpage><lpage>44</lpage><pub-id pub-id-type="pmid">26507310</pub-id></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sref11"><person-group person-group-type="author"><name><surname>Crutch</surname><given-names>S.J.</given-names></name><name><surname>Schott</surname><given-names>J.M.</given-names></name><name><surname>Rabinovici</surname><given-names>G.D.</given-names></name><name><surname>Boeve</surname><given-names>B.F.</given-names></name><name><surname>Cappa</surname><given-names>S.F.</given-names></name><name><surname>Dickerson</surname><given-names>B.C.</given-names></name></person-group><article-title>Shining a light on posterior cortical atrophy</article-title><source>Alzheimers Dement</source><volume>9</volume><year>2013</year><fpage>463</fpage><lpage>465</lpage><pub-id pub-id-type="pmid">23274153</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal" id="sref12"><person-group person-group-type="author"><name><surname>Mendez</surname><given-names>M.F.</given-names></name><name><surname>Ghajarania</surname><given-names>M.</given-names></name><name><surname>Perryman</surname><given-names>K.M.</given-names></name></person-group><article-title>Posterior cortical atrophy: clinical characteristics and differences compared to Alzheimer's disease</article-title><source>Dement Geriatr Cogn Disord</source><volume>14</volume><year>2002</year><fpage>33</fpage><lpage>40</lpage><pub-id pub-id-type="pmid">12053130</pub-id></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal" id="sref13"><person-group person-group-type="author"><name><surname>Delaneau</surname><given-names>O.</given-names></name><name><surname>Zagury</surname><given-names>J.F.</given-names></name><name><surname>Marchini</surname><given-names>J.</given-names></name></person-group><article-title>Improved whole-chromosome phasing for disease and population genetic studies</article-title><source>Nat Methods</source><volume>10</volume><year>2013</year><fpage>5</fpage><lpage>6</lpage><pub-id pub-id-type="pmid">23269371</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="journal" id="sref14"><person-group person-group-type="author"><name><surname>Howie</surname><given-names>B.N.</given-names></name><name><surname>Donnelly</surname><given-names>P.</given-names></name><name><surname>Marchini</surname><given-names>J.</given-names></name></person-group><article-title>A flexible and accurate genotype imputation method for the next generation of genome-wide association studies</article-title><source>PLoS Genet</source><volume>5</volume><year>2009</year><fpage>e1000529</fpage><pub-id pub-id-type="pmid">19543373</pub-id></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal" id="sref15"><person-group person-group-type="author"><name><surname>Marchini</surname><given-names>J.</given-names></name><name><surname>Howie</surname><given-names>B.</given-names></name></person-group><article-title>Genotype imputation for genome-wide association studies</article-title><source>Nat Rev Genet</source><volume>11</volume><year>2010</year><fpage>499</fpage><lpage>511</lpage><pub-id pub-id-type="pmid">20517342</pub-id></element-citation></ref><ref id="bib16"><label>16</label><element-citation publication-type="journal" id="sref16"><person-group person-group-type="author"><name><surname>Marchini</surname><given-names>J.</given-names></name><name><surname>Howie</surname><given-names>B.</given-names></name><name><surname>Myers</surname><given-names>S.</given-names></name><name><surname>McVean</surname><given-names>G.</given-names></name><name><surname>Donnelly</surname><given-names>P.</given-names></name></person-group><article-title>A new multipoint method for genome-wide association studies by imputation of genotypes</article-title><source>Nat Genet</source><volume>39</volume><year>2007</year><fpage>906</fpage><lpage>913</lpage><pub-id pub-id-type="pmid">17572673</pub-id></element-citation></ref><ref id="bib17"><label>17</label><element-citation publication-type="journal" id="sref17"><person-group person-group-type="author"><name><surname>Purcell</surname><given-names>S.</given-names></name><name><surname>Neale</surname><given-names>B.</given-names></name><name><surname>Todd-Brown</surname><given-names>K.</given-names></name><name><surname>Thomas</surname><given-names>L.</given-names></name><name><surname>Ferreira</surname><given-names>M.A.</given-names></name><name><surname>Bender</surname><given-names>D.</given-names></name></person-group><article-title>PLINK: a tool set for whole-genome association and population-based linkage analyses</article-title><source>Am J Hum Genet</source><volume>81</volume><year>2007</year><fpage>559</fpage><lpage>575</lpage><pub-id pub-id-type="pmid">17701901</pub-id></element-citation></ref><ref id="bib18"><label>18</label><element-citation publication-type="journal" id="sref18"><person-group person-group-type="author"><name><surname>Lambert</surname><given-names>J.C.</given-names></name><name><surname>Ibrahim-Verbaas</surname><given-names>C.A.</given-names></name><name><surname>Harold</surname><given-names>D.</given-names></name><name><surname>Naj</surname><given-names>A.C.</given-names></name><name><surname>Sims</surname><given-names>R.</given-names></name><name><surname>Bellenguez</surname><given-names>C.</given-names></name></person-group><article-title>Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease</article-title><source>Nat Genet</source><volume>45</volume><year>2013</year><fpage>1452</fpage><lpage>1458</lpage><pub-id pub-id-type="pmid">24162737</pub-id></element-citation></ref><ref id="bib19"><label>19</label><element-citation publication-type="journal" id="sref19"><person-group person-group-type="author"><name><surname>Bras</surname><given-names>J.</given-names></name><name><surname>Guerreiro</surname><given-names>R.</given-names></name><name><surname>Darwent</surname><given-names>L.</given-names></name></person-group><article-title>Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies</article-title><source>Hum Mol Genet</source><volume>23</volume><year>2014</year><fpage>6139</fpage><lpage>6146</lpage><pub-id pub-id-type="pmid">24973356</pub-id></element-citation></ref><ref id="bib20"><label>20</label><element-citation publication-type="journal" id="sref20"><person-group person-group-type="author"><name><surname>Corder</surname><given-names>E.H.</given-names></name><name><surname>Saunders</surname><given-names>A.M.</given-names></name><name><surname>Strittmatter</surname><given-names>W.J.</given-names></name></person-group><article-title>Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families</article-title><source>Science</source><volume>261</volume><year>1993</year><fpage>921</fpage><lpage>923</lpage><pub-id pub-id-type="pmid">8346443</pub-id></element-citation></ref><ref id="bib21"><label>21</label><element-citation publication-type="journal" id="sref21"><person-group person-group-type="author"><name><surname>Mead</surname><given-names>S.</given-names></name><name><surname>Poulter</surname><given-names>M.</given-names></name><name><surname>Uphill</surname><given-names>J.</given-names></name><name><surname>Beck</surname><given-names>J.</given-names></name><name><surname>Whitfield</surname><given-names>J.</given-names></name><name><surname>Webb</surname><given-names>T.E.</given-names></name></person-group><article-title>Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study</article-title><source>Lancet Neurol</source><volume>8</volume><year>2009</year><fpage>57</fpage><lpage>66</lpage><pub-id pub-id-type="pmid">19081515</pub-id></element-citation></ref><ref id="bib22"><label>22</label><element-citation publication-type="journal" id="sref22"><person-group person-group-type="author"><name><surname>Klein</surname><given-names>R.J.</given-names></name><name><surname>Zeiss</surname><given-names>C.</given-names></name><name><surname>Chew</surname><given-names>E.Y.</given-names></name><name><surname>Tsai</surname><given-names>J.Y.</given-names></name><name><surname>Sackler</surname><given-names>R.S.</given-names></name><name><surname>Haynes</surname><given-names>C.</given-names></name></person-group><article-title>Complement factor H polymorphism in age-related macular degeneration</article-title><source>Science</source><volume>308</volume><year>2005</year><fpage>385</fpage><lpage>389</lpage><pub-id pub-id-type="pmid">15761122</pub-id></element-citation></ref><ref id="bib23"><label>23</label><element-citation publication-type="journal" id="sref23"><person-group person-group-type="author"><name><surname>Thambisetty</surname><given-names>M.</given-names></name><name><surname>An</surname><given-names>Y.</given-names></name><name><surname>Tanaka</surname><given-names>T.</given-names></name></person-group><article-title>Alzheimer's disease risk genes and the age-at-onset phenotype</article-title><source>Neurobiol Aging</source><volume>34</volume><year>2013</year><fpage>2696.e1</fpage><lpage>2696.e5</lpage><pub-id pub-id-type="pmid">23870418</pub-id></element-citation></ref><ref id="bib24"><label>24</label><element-citation publication-type="journal" id="sref24"><person-group person-group-type="author"><name><surname>Mori</surname><given-names>E.</given-names></name><name><surname>Lee</surname><given-names>K.</given-names></name><name><surname>Yasuda</surname><given-names>M.</given-names></name><name><surname>Hashimoto</surname><given-names>M.</given-names></name><name><surname>Kazui</surname><given-names>H.</given-names></name><name><surname>Hirono</surname><given-names>N.</given-names></name></person-group><article-title>Accelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E epsilon4 allele</article-title><source>Ann Neurol</source><volume>51</volume><year>2002</year><fpage>209</fpage><lpage>214</lpage><pub-id pub-id-type="pmid">11835377</pub-id></element-citation></ref><ref id="bib25"><label>25</label><element-citation publication-type="journal" id="sref25"><person-group person-group-type="author"><name><surname>van der Flier</surname><given-names>W.M.</given-names></name><name><surname>Pijnenburg</surname><given-names>Y.A.</given-names></name><name><surname>Fox</surname><given-names>N.C.</given-names></name><name><surname>Scheltens</surname><given-names>P.</given-names></name></person-group><article-title>Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE ɛ4 allele</article-title><source>Lancet Neurol</source><volume>10</volume><year>2011</year><fpage>280</fpage><lpage>288</lpage><pub-id pub-id-type="pmid">21185234</pub-id></element-citation></ref><ref id="bib26"><label>26</label><element-citation publication-type="journal" id="sref26"><person-group person-group-type="author"><name><surname>Crehan</surname><given-names>H.</given-names></name><name><surname>Holton</surname><given-names>P.</given-names></name><name><surname>Wray</surname><given-names>S.</given-names></name><name><surname>Pocock</surname><given-names>J.</given-names></name><name><surname>Guerreiro</surname><given-names>R.</given-names></name><name><surname>Hardy</surname><given-names>J.</given-names></name></person-group><article-title>Complement receptor 1 (CR1) and Alzheimer's disease</article-title><source>Immunobiology</source><volume>217</volume><year>2012</year><fpage>244</fpage><lpage>250</lpage><pub-id pub-id-type="pmid">21840620</pub-id></element-citation></ref><ref id="bib27"><label>27</label><element-citation publication-type="journal" id="sref27"><person-group person-group-type="author"><name><surname>Prokic</surname><given-names>I.</given-names></name><name><surname>Cowling</surname><given-names>B.S.</given-names></name><name><surname>Laporte</surname><given-names>J.</given-names></name></person-group><article-title>Amphiphysin 2 (BIN1) in physiology and diseases</article-title><source>J Mol Med</source><volume>92</volume><year>2014</year><fpage>453</fpage><lpage>463</lpage><pub-id pub-id-type="pmid">24590001</pub-id></element-citation></ref><ref id="bib28"><label>28</label><element-citation publication-type="journal" id="sref28"><person-group person-group-type="author"><name><surname>Rosenthal</surname><given-names>S.L.</given-names></name><name><surname>Kamboh</surname><given-names>M.I.</given-names></name></person-group><article-title>Late-Onset Alzheimer's Disease Genes and the Potentially Implicated Pathways</article-title><source>Curr Genet Med Rep</source><volume>2</volume><year>2014</year><fpage>85</fpage><lpage>101</lpage><pub-id pub-id-type="pmid">24829845</pub-id></element-citation></ref><ref id="bib29"><label>29</label><element-citation publication-type="journal" id="sref29"><person-group person-group-type="author"><name><surname>Pagnamenta</surname><given-names>A.T.</given-names></name><name><surname>Bacchelli</surname><given-names>E.</given-names></name><name><surname>de Jonge</surname><given-names>M.V.</given-names></name><name><surname>Mirza</surname><given-names>G.</given-names></name><name><surname>Scerri</surname><given-names>T.S.</given-names></name><name><surname>Minopoli</surname><given-names>F.</given-names></name></person-group><article-title>Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia</article-title><source>Biol Psychiatry</source><volume>68</volume><year>2010</year><fpage>320</fpage><lpage>328</lpage><pub-id pub-id-type="pmid">20346443</pub-id></element-citation></ref><ref id="bib30"><label>30</label><element-citation publication-type="journal" id="sref30"><person-group person-group-type="author"><name><surname>Lagali</surname><given-names>P.S.</given-names></name><name><surname>Kakuk</surname><given-names>L.E.</given-names></name><name><surname>Griesinger</surname><given-names>I.B.</given-names></name><name><surname>Wong</surname><given-names>P.W.</given-names></name><name><surname>Ayyagari</surname><given-names>R.</given-names></name></person-group><article-title>Identification and characterization of C6orf37, a novel candidate human retinal disease gene on chromosome 6q14</article-title><source>Biochem Biophys Res Commun</source><volume>293</volume><year>2002</year><fpage>356</fpage><lpage>365</lpage><pub-id pub-id-type="pmid">12054608</pub-id></element-citation></ref><ref id="bib31"><label>31</label><element-citation publication-type="journal" id="sref31"><person-group person-group-type="author"><name><surname>Barragán</surname><given-names>I.</given-names></name><name><surname>Borrego</surname><given-names>S.</given-names></name><name><surname>Abd El-Aziz</surname><given-names>M.M.</given-names></name><name><surname>El-Ashry</surname><given-names>M.F.</given-names></name><name><surname>Abu-Safieh</surname><given-names>L.</given-names></name><name><surname>Bhattacharya</surname><given-names>S.S.</given-names></name></person-group><article-title>Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs</article-title><source>Ann Hum Genet</source><volume>72</volume><year>2008</year><fpage>26</fpage><lpage>34</lpage><pub-id pub-id-type="pmid">17803723</pub-id></element-citation></ref><ref id="bib32"><label>32</label><element-citation publication-type="journal" id="sref32"><person-group person-group-type="author"><name><surname>Bagnard</surname><given-names>D.</given-names></name><name><surname>Thomasset</surname><given-names>N.</given-names></name><name><surname>Lohrum</surname><given-names>M.</given-names></name><name><surname>Püschel</surname><given-names>A.W.</given-names></name><name><surname>Bolz</surname><given-names>J.</given-names></name></person-group><article-title>Spatial distributions of guidance molecules regulate chemorepulsion and chemoattraction of growth cones</article-title><source>J Neurosci</source><volume>20</volume><year>2000</year><fpage>1030</fpage><lpage>1035</lpage><pub-id pub-id-type="pmid">10648708</pub-id></element-citation></ref><ref id="bib33"><label>33</label><element-citation publication-type="journal" id="sref33"><person-group person-group-type="author"><name><surname>Sharma</surname><given-names>A.</given-names></name><name><surname>LeVaillant</surname><given-names>C.J.</given-names></name><name><surname>Plant</surname><given-names>G.W.</given-names></name><name><surname>Harvey</surname><given-names>A.R.</given-names></name></person-group><article-title>Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus</article-title><source>BMC Dev Biol</source><volume>14</volume><year>2014</year><fpage>34</fpage><pub-id pub-id-type="pmid">25062604</pub-id></element-citation></ref><ref id="bib34"><label>34</label><element-citation publication-type="journal" id="sref34"><person-group person-group-type="author"><name><surname>Steup</surname><given-names>A.</given-names></name><name><surname>Lohrum</surname><given-names>M.</given-names></name><name><surname>Hamscho</surname><given-names>N.</given-names></name><name><surname>Savaskan</surname><given-names>N.E.</given-names></name><name><surname>Ninnemann</surname><given-names>O.</given-names></name><name><surname>Nitsch</surname><given-names>R.</given-names></name></person-group><article-title>Sema3C and Netrin-1 Differentially Affect Axon Growth in the Hippocampal Formation</article-title><source>Mol Cell Neurosci</source><volume>15</volume><year>2000</year><fpage>141</fpage><lpage>155</lpage><pub-id pub-id-type="pmid">10673323</pub-id></element-citation></ref><ref id="bib35"><label>35</label><element-citation publication-type="journal" id="sref35"><person-group person-group-type="author"><name><surname>Dutar</surname><given-names>P.</given-names></name><name><surname>Bassant</surname><given-names>M.H.</given-names></name><name><surname>Senut</surname><given-names>M.C.</given-names></name></person-group><article-title>The septohippocampal pathway: structure and function of a central cholinergic system</article-title><source>Physiol Rev</source><volume>75</volume><year>1995</year><fpage>393</fpage><lpage>427</lpage><pub-id pub-id-type="pmid">7724668</pub-id></element-citation></ref><ref id="bib36"><label>36</label><element-citation publication-type="journal" id="sref36"><person-group person-group-type="author"><name><surname>Richiardi</surname><given-names>J.</given-names></name><name><surname>Altmann</surname><given-names>A.</given-names></name><name><surname>Milazzo</surname><given-names>A.C.</given-names></name><name><surname>Chang</surname><given-names>C.</given-names></name><name><surname>Chakravarty</surname><given-names>M.M.</given-names></name><name><surname>Banaschewski</surname><given-names>T.</given-names></name></person-group><article-title>Brain Networks. Correlated gene expression supports synchronous activity in brain networks</article-title><source>Science</source><volume>348</volume><year>2015</year><fpage>1241</fpage><lpage>1244</lpage><pub-id pub-id-type="pmid">26068849</pub-id></element-citation></ref></ref-list><sec id="appsec1" sec-type="supplementary-material"><title>Supplementary data</title><p><supplementary-material content-type="local-data" id="ec1"><caption><title>Supplementary Figures 1 and 2 and Supplementary Tables 1 and 2</title></caption><media xlink:href="mmc1.docx"></media></supplementary-material></p></sec><ack id="ack0010"><title>Acknowledgments</title><p>We acknowledge the support of the Alzheimer's Association's International Society to Advance Alzheimer's Research and Treatment (ISTAART), Alzheimer's Research UK, the UK Alzheimer's Society and the Raena Frankel-Pollen Fund. This work was supported by the <funding-source id="gs1">NIHR UCL/UCLH Biomedical Research Centre</funding-source>, <funding-source id="gs2">the NIHR Queen Square Dementia Biomedical Research Unit</funding-source>, <funding-source id="gs3">the Wolfson Foundation</funding-source>, and <funding-source id="gs4">the UK Medical Research Council</funding-source>. The Dementia Research Centre is an Alzheimer's Research UK Coordinating Center. N.C.F. and M.N.R. are NIHR senior investigators. N.S.R. is in receipt of a Brain Exit Fellowship. J.T.B. receives funding from the UK Alzheimer's Society. This work was also supported by the <funding-source id="gs5">Medical Research Council Dementias Platform UK</funding-source> (MR/L023784/1 and MR/009076/1); <funding-source id="gs6">Alzheimer's Research UK</funding-source> (Senior Research Fellowship to S.C., Research Fellowship to T.S.); <funding-source id="gs7">the Dunhill Medical Trust</funding-source> (grant number R337/0214 to S.C.); <funding-source id="gs8">ESRC/NIHR</funding-source> (ES/K006711/1 to S.C.); <funding-source id="gs9">EPSRC</funding-source> (EP/M006093/1 to S.C.); <funding-source id="gs10">Alzheimer's Association</funding-source> (MNIRGD 2013 award to M.M.C.); <funding-source id="gs11">Mayo Alzheimer's Disease Research Center</funding-source> (P50 AG0016574 to D.W.D., N.E.-T., N.R.G.-R., B.F.B., D.S.K., R.C.P.); <funding-source id="gs12">National Institute on Aging</funding-source> (R01 AG032990 and U01 AG046139 to N.E.-T.; R01-AG045611 to G.D.R.; and P50-AG023501 to B.L.M. and G.D.R.); <funding-source id="gs13">National Institute of Neurological Disorders and Stroke</funding-source> (R01 NS080820 to N.E.-T.); <funding-source id="gs14">John Douglas French Alzheimer's Foundation</funding-source> (to G.D.R., B.L.M.); and <funding-source id="gs15">State of California Department of Health Services Alzheimer's Disease Research Centre of California</funding-source> (04-33516, B.L.M.). D.G. and E.S. are supported by Italian Ministry of Health (Ricerca Corrente). W.M.v.d.F., P.S. receive funding from PERADES-JPND. E.L. receives funding from Stichting Dioraphte. Case ascertainment in Australia was funded by grants from the National Health and Medical Research Council of Australia (NHMRC program grant #1037746) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Node (#CE110001021); G.H. is a NHMRC senior principal research fellow (#1079679). We would like to thank the participants in the Framingham, Geisinger, WTCCC, and KORA studies used as controls in this article. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This article was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. Samples and data in this study were also provided by the Geisinger MyCode Project. Funding for the MyCode project was provided by a grant from Commonwealth of Pennsylvania and the Clinic Research Fund of Geisinger Clinic. Funding support for the genotyping of the MyCode cohort was provided by a Geisinger Clinic operating funds and an award from the Clinic Research Fund. The data sets used for the analyses described in this article were obtained from dbGaP at <ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/gap" id="intref0020">http://www.ncbi.nlm.nih.gov/gap</ext-link> through dbGaP accession number phs000381.v1.p1. This study also makes use of the data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from <ext-link ext-link-type="uri" xlink:href="http://www.wtccc.org.uk" id="intref0025">www.wtccc.org.uk</ext-link>. Funding for the project was provided by the Wellcome Trust under award 076113.</p></ack><fn-group><fn id="appsec2" fn-type="supplementary-material"><p>Supplementary data related to this article can be found online at <ext-link ext-link-type="doi" xlink:href="10.1016/j.jalz.2016.01.010" id="intref0030">http://dx.doi.org/10.1016/j.jalz.2016.01.010</ext-link>.</p></fn></fn-group></back><floats-group><fig id="fig1"><label>Fig. 1</label><caption><p>Manhattan plot of autosomes with the threshold for genome-wide significance (<italic>P</italic> < 5 × 10<sup>−8</sup>) indicated by the red line. Four loci achieved statistical significance at <italic>APOE</italic> (chromosome 19), <italic>SEMA3C</italic> (chromosome 7), <italic>FAM46A</italic> (chromosome 6), and <italic>CNTNAP5</italic> (chromosome 2).</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Fig. 2</label><caption><p>SNP annotation and proxy (SNAP) plots for five regions of interest showing significance in either known genetic loci for AD (A, B) or in the exploratory GWAS (A,C,D,E). These plots illustrate the statistical evidence of association at a locus together with information about nearby genes and linkage disequilibrium between the most strongly associated SNP and its neighbors on the chromosome.</p></caption><graphic xlink:href="gr2"></graphic></fig><table-wrap id="tbl1" position="float"><label>Table 1</label><caption><p>Clinical criteria for PCA</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Tang-Wai et al, 2004 <xref rid="bib5" ref-type="bibr">[5]</xref></th><th>Mendez et al, 2002 <xref rid="bib11" ref-type="bibr">[11]</xref></th></tr></thead><tbody><tr><td><list list-type="simple"><list-item id="u0010"><p>Core features<list list-type="simple"><list-item id="u0015"><p>Insidious onset and gradual progression</p></list-item><list-item id="u0020"><p>Presentation of visual complaints in the absence of significant primary ocular disease</p></list-item><list-item id="u0025"><p>Relative preservation of anterograde memory and insight early in the disorder</p></list-item><list-item id="u0030"><p>Disabling visual impairment throughout the disorder</p></list-item><list-item id="u0035"><p>Absence of stroke or tumor</p></list-item><list-item id="u0040"><p>Absence of early parkinsonism and hallucinations</p></list-item><list-item id="u0045"><p><italic>Any of the following findings</italic></p></list-item><list-item id="u0050"><p>Simultanagnosia with or without optic ataxia or ocular apraxia</p></list-item><list-item id="u0055"><p>Constructional dyspraxia</p></list-item><list-item id="u0060"><p>Visual field defect</p></list-item><list-item id="u0065"><p>Environmental disorientation</p></list-item><list-item id="u0070"><p>Any of the elements of Gerstmann syndrome</p></list-item></list></p></list-item><list-item id="u0075"><p>Supportive features<list list-type="simple"><list-item id="u0080"><p>Alexia</p></list-item><list-item id="u0085"><p>Presenile onset</p></list-item><list-item id="u0090"><p>Ideomotor or dressing apraxia</p></list-item><list-item id="u0095"><p>Prosopagnosia</p></list-item></list></p></list-item><list-item id="u0100"><p>Investigations<list list-type="simple"><list-item id="u0105"><p>Neuropsychological deficits referable to parietal and/or occipital regions</p></list-item><list-item id="u0110"><p>Focal or asymmetric atrophy in parietal and/or occipital regions on structural imaging</p></list-item><list-item id="u0115"><p>Focal or asymmetric hypoperfusion/hypometabolism in parietal and/or occipital regions on functional imaging.</p></list-item></list></p></list-item></list></td><td><list list-type="simple"><list-item id="u0120"><p>Core diagnostic features (all must be present)<list list-type="simple"><list-item id="u0125"><p>Insidious onset and gradual progression</p></list-item><list-item id="u0130"><p>Presentation with visual complaints with intact primary visual functions</p></list-item><list-item id="u0135"><p>Evidence of predominant complex visual disorder on examination</p></list-item><list-item id="u0140"><p>Elements of Balint's syndrome</p></list-item><list-item id="u0145"><p>Visual agnosia</p></list-item><list-item id="u0150"><p>Dressing apraxia</p></list-item><list-item id="u0155"><p>Environmental disorientation</p></list-item><list-item id="u0160"><p>Proportionally less impaired deficits in memory and verbal fluency</p></list-item><list-item id="u0165"><p>Relatively preserved insight with or without depression</p></list-item></list></p></list-item><list-item id="u0170"><p>Supportive diagnostic features<list list-type="simple"><list-item id="u0175"><p>Presenile onset</p></list-item><list-item id="u0180"><p>Alexia</p></list-item><list-item id="u0185"><p>Elements of Gerstmann's syndrome</p></list-item><list-item id="u0190"><p>Ideomotor apraxia</p></list-item><list-item id="u0195"><p>Physical examination within normal limits</p></list-item></list></p></list-item><list-item id="u0200"><p>Investigations<list list-type="simple"><list-item id="u0205"><p>Neuropsychology: predominantly impaired perceptual deficits</p></list-item><list-item id="u0210"><p>Brain imaging: predominantly occipitoparietal abnormality (especially on functional neuroimaging) with relative sparing of frontal and mesiotemporal regions.</p></list-item></list></p></list-item></list></td></tr></tbody></table></table-wrap><table-wrap id="tbl2" position="float"><label>Table 2</label><caption><p>Clinical features and demographics</p></caption><table frame="hsides" rules="groups"><tbody><tr><td>Total number of DNA samples received</td><td>302</td></tr><tr><td>Number (%) male</td><td align="char">124 (41%)</td></tr><tr><td>Mean ± SD age at onset (y)</td><td>58.9 ± 6.9</td></tr><tr><td>Number (%) with young onset dementia (onset <65 y)</td><td align="char">249 (83%)</td></tr><tr><td>Number with biomarker/path evidence for AD<xref rid="tbl2fnlowast" ref-type="table-fn">∗</xref></td><td align="char">82 (27%)</td></tr><tr><td>Number (%) with known age of death</td><td>34</td></tr><tr><td>Mean ± SD age at death (y)</td><td>67.9 ± 7.7</td></tr><tr><td colspan="2"><inline-graphic xlink:href="fx1.gif"></inline-graphic><break></break>9 samples failed genetic QC<break></break><inline-graphic xlink:href="fx1.gif"></inline-graphic></td></tr><tr><td>Total number of DNA samples passing QC and entering analysis</td><td>293</td></tr><tr><td>Number (%) male</td><td align="char">120 (41%)</td></tr><tr><td>Mean ± SD age at onset (y)</td><td>58.8 ± 6.9</td></tr><tr><td>Number (%) with young onset dementia (onset <65 y)</td><td align="char">243 (83%)</td></tr><tr><td>Number with biomarker/path evidence for AD<xref rid="tbl2fnlowast" ref-type="table-fn">∗</xref></td><td align="char">77 (26%)</td></tr><tr><td>Number (%) with known age of death</td><td>33</td></tr><tr><td>Mean ± SD age at death (y)</td><td>67.8 ± 7.8</td></tr></tbody></table><table-wrap-foot><fn id="tbl2fnlowast"><label>∗</label><p id="ntpara0010">No individual with biomarker/path evidence for a non-AD diagnosis was included.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl3" position="float"><label>Table 3</label><caption><p>Results of the main analysis for candidate SNPs which were discovered in typical AD (ref <xref rid="bib16" ref-type="bibr">[16]</xref>, except <sup>∗</sup>Seshadri et al. JAMA 2010:303; 1832–40, <sup>†</sup>Hollingworth et al. Nat Genet 2011:43:429–35) or DLB <xref rid="bib17" ref-type="bibr">[17]</xref></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Candidate SNP</th><th>Chr</th><th>Nearest gene</th><th>Typical AD/DLB OR</th><th>PCA vs control <italic>P</italic> value</th><th>PCA OR</th><th>PCA OR CI</th><th><italic>P</italic> Value for comparison of OR (PCA vs typical AD)</th><th>Cases MAF</th><th>Control MAF</th></tr></thead><tbody><tr><td>rs3818361</td><td align="char">1</td><td><italic>CR1</italic></td><td align="char">1.17</td><td>6.71E−04</td><td align="char">1.38</td><td align="char">(1.14–1.67)</td><td align="char">.09</td><td align="char">0.24</td><td align="char">0.19</td></tr><tr><td>rs744373</td><td align="char">2</td><td><italic>BIN1</italic></td><td align="char">1.17</td><td align="char">0.04</td><td align="char">1.20</td><td align="char">(1.01–1.43)</td><td align="char">.77</td><td align="char">0.32</td><td align="char">0.28</td></tr><tr><td>rs35349669</td><td align="char">2</td><td><italic>INPP5D</italic></td><td align="char">1.08</td><td align="char">0.21</td><td align="char">0.89</td><td align="char">(0.75–1.04)</td><td align="char">.02</td><td align="char">0.46</td><td align="char">0.49</td></tr><tr><td>rs6825004</td><td align="char">4</td><td><italic>SCARB2</italic></td><td align="char">0.78</td><td align="char">0.42</td><td align="char">0.92</td><td align="char">(0.77–1.1)</td><td align="char">.38</td><td align="char">0.29</td><td align="char">0.31</td></tr><tr><td>rs7687945</td><td align="char">4</td><td><italic>SNCA</italic></td><td align="char">0.75</td><td align="char">0.92</td><td align="char">1.00</td><td align="char">(0.85–1.18)</td><td align="char">.08</td><td align="char">0.49</td><td align="char">0.49</td></tr><tr><td>rs190982</td><td align="char">5</td><td><italic>MEF2C</italic></td><td align="char">0.93</td><td align="char">0.66</td><td align="char">0.99</td><td align="char">(0.83–1.18)</td><td align="char">.50</td><td align="char">0.40</td><td align="char">0.40</td></tr><tr><td>rs10948363</td><td align="char">6</td><td><italic>CD2AP</italic></td><td align="char">1.10</td><td align="char">0.67</td><td align="char">0.97</td><td align="char">(0.8–1.17)</td><td align="char">.19</td><td align="char">0.27</td><td align="char">0.27</td></tr><tr><td>rs11767557</td><td align="char">7</td><td><italic>EPHA1</italic></td><td align="char">0.90</td><td align="char">0.39</td><td align="char">0.92</td><td align="char">(0.74–1.13)</td><td align="char">.73</td><td align="char">0.19</td><td align="char">0.20</td></tr><tr><td>rs2718058</td><td align="char">7</td><td><italic>NME8</italic></td><td align="char">0.93</td><td align="char">0.17</td><td align="char">1.12</td><td align="char">(0.95–1.33)</td><td align="char">.03</td><td align="char">0.39</td><td align="char">0.36</td></tr><tr><td>rs1476679</td><td align="char">7</td><td><italic>ZCWPW1</italic></td><td align="char">0.91</td><td align="char">0.73</td><td align="char">1.05</td><td align="char">(0.88–1.25)</td><td align="char">.12</td><td align="char">0.31</td><td align="char">0.30</td></tr><tr><td>rs11136000</td><td align="char">8</td><td><italic>CLU</italic></td><td align="char">0.87</td><td align="char">0.27</td><td align="char">0.91</td><td align="char">(0.77–1.09)</td><td align="char">.58</td><td align="char">0.37</td><td align="char">0.40</td></tr><tr><td>rs28834970</td><td align="char">8</td><td><italic>PTK2B</italic></td><td align="char">1.10</td><td align="char">0.27</td><td align="char">1.10</td><td align="char">(0.93–1.3)</td><td align="char">.98</td><td align="char">0.37</td><td align="char">0.35</td></tr><tr><td>rs10838725</td><td align="char">11</td><td><italic>CELF1</italic></td><td align="char">1.08</td><td align="char">0.98</td><td align="char">1.01</td><td align="char">(0.84–1.2)</td><td align="char">.45</td><td align="char">0.32</td><td align="char">0.31</td></tr><tr><td>rs670139<sup>†</sup></td><td align="char">11</td><td><italic>MS4A4E</italic></td><td align="char">1.08</td><td align="char">0.77</td><td align="char">0.97</td><td align="char">(0.82–1.14)</td><td align="char">.19</td><td align="char">0.40</td><td align="char">0.41</td></tr><tr><td>rs983392</td><td align="char">11</td><td><italic>MS4A6A</italic></td><td align="char">0.90</td><td align="char">0.71</td><td align="char">1.04</td><td align="char">(0.88–1.22)</td><td align="char">.09</td><td align="char">0.42</td><td align="char">0.41</td></tr><tr><td>rs3851179</td><td align="char">11</td><td><italic>PICALM</italic></td><td align="char">0.87</td><td align="char">0.39</td><td align="char">0.94</td><td align="char">(0.79–1.11)</td><td align="char">.40</td><td align="char">0.35</td><td align="char">0.37</td></tr><tr><td>rs11218343</td><td align="char">11</td><td><italic>SORL1</italic></td><td align="char">0.77</td><td align="char">0.57</td><td align="char">0.81</td><td align="char">(0.4–1.65)</td><td align="char">.88</td><td align="char">0.01</td><td align="char">0.02</td></tr><tr><td>rs17125944</td><td align="char">14</td><td><italic>FERMT2</italic></td><td align="char">1.14</td><td align="char">0.73</td><td align="char">0.94</td><td align="char">(0.7–1.27)</td><td align="char">.21</td><td align="char">0.08</td><td align="char">0.09</td></tr><tr><td>rs10498633</td><td align="char">14</td><td><italic>SLC24A4</italic><break></break><italic>RIN3</italic></td><td align="char">0.91</td><td align="char">0.14</td><td align="char">0.86</td><td align="char">(0.7–1.06)</td><td align="char">.62</td><td align="char">0.20</td><td align="char">0.23</td></tr><tr><td>rs3764650</td><td align="char">19</td><td><italic>ABCA7</italic></td><td align="char">1.20</td><td align="char">0.02</td><td align="char">1.39</td><td align="char">(1.07–1.8)</td><td align="char">.28</td><td align="char">0.12</td><td align="char">0.09</td></tr><tr><td>rs2075650</td><td align="char">19</td><td><italic>APOE</italic></td><td align="char">2.83</td><td>6.24E−14</td><td align="char">2.03</td><td align="char">(1.68–2.46)</td><td align="char">.0007</td><td align="char">0.25</td><td align="char">0.14</td></tr><tr><td>rs3865444<sup>†</sup></td><td align="char">19</td><td><italic>CD33</italic></td><td align="char">0.91</td><td align="char">0.69</td><td align="char">0.95</td><td align="char">(0.8–1.14)</td><td align="char">.61</td><td align="char">0.30</td><td align="char">0.31</td></tr><tr><td>rs597668<sup>∗</sup></td><td align="char">19</td><td><italic>EXOC3L2</italic><break></break><italic>BLOC1S3</italic><break></break><italic>MARK4</italic></td><td align="char">1.18</td><td align="char">0.59</td><td align="char">1.04</td><td align="char">(0.84–1.3)</td><td align="char">.30</td><td align="char">0.17</td><td align="char">0.16</td></tr><tr><td>rs7274581</td><td align="char">20</td><td><italic>CASS4</italic></td><td align="char">0.88</td><td align="char">0.52</td><td align="char">1.12</td><td align="char">(0.85–1.48)</td><td align="char">.09</td><td align="char">0.10</td><td align="char">0.09</td></tr></tbody></table><table-wrap-foot><fn><p>OR, odds ratio; MAF, minor allele frequency; CI, confidence interval.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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