A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.
Identifieur interne : 002D50 ( PubMed/Curation ); précédent : 002D49; suivant : 002D51A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.
Auteurs : Pascual Sanchez-Juan [Espagne] ; Matthew T. Bishop [Royaume-Uni] ; Gabor G. Kovacs [Autriche] ; Miguel Calero [Espagne] ; Yurii S. Aulchenko [Russie] ; Anna Ladogana [Italie] ; Alison Boyd [Australie] ; Victoria Lewis [Australie] ; Claudia Ponto [Allemagne] ; Olga Calero ; Anna Poleggi [Italie] ; Ángel Carracedo ; Sven J. Van Der Lee [Pays-Bas] ; Thomas Ströbel [Autriche] ; Fernando Rivadeneira [Pays-Bas] ; Albert Hofman [Pays-Bas] ; Stéphane Haïk [France] ; Onofre Combarros [Espagne] ; José Berciano [Espagne] ; Andre G. Uitterlinden [Pays-Bas] ; Steven J. Collins [Australie] ; Herbert Budka [Autriche] ; Jean-Philippe Brandel [France] ; Jean Louis Laplanche [France] ; Maurizio Pocchiari [Italie] ; Inga Zerr [Allemagne] ; Richard S G. Knight [Royaume-Uni] ; Robert G. Will [Royaume-Uni] ; Cornelia M. Van Duijn [Pays-Bas]Source :
- PloS one [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Prions, Receptors, Metabotropic Glutamate.
- chemical : Prion Proteins.
- genetics : Creutzfeldt-Jakob Syndrome.
- methods : Genome-Wide Association Study.
- Case-Control Studies, Germany, Humans, Netherlands, Polymorphism, Single Nucleotide, Signal Transduction, United Kingdom.
Abstract
We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis.
DOI: 10.1371/journal.pone.0123654
PubMed: 25918841
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Olga Calero<affiliation><nlm:affiliation>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</nlm:affiliation><wicri:noCountry code="no comma">Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Fundación Pública Galega de Medicina Xenómica, CIBERER, Grupo de Medicina Xenómica-Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.</title><author><name sortKey="Sanchez Juan, Pascual" sort="Sanchez Juan, Pascual" uniqKey="Sanchez Juan P" first="Pascual" last="Sanchez-Juan">Pascual Sanchez-Juan</name><affiliation wicri:level="1"><nlm:affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander</wicri:regionArea></affiliation></author><author><name sortKey="Bishop, Matthew T" sort="Bishop, Matthew T" uniqKey="Bishop M" first="Matthew T" last="Bishop">Matthew T. Bishop</name><affiliation wicri:level="1"><nlm:affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Kovacs, Gabor G" sort="Kovacs, Gabor G" uniqKey="Kovacs G" first="Gabor G" last="Kovacs">Gabor G. 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Spain; Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Aulchenko, Yurii S" sort="Aulchenko, Yurii S" uniqKey="Aulchenko Y" first="Yurii S" last="Aulchenko">Yurii S. Aulchenko</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk</wicri:regionArea></affiliation></author><author><name sortKey="Ladogana, Anna" sort="Ladogana, Anna" uniqKey="Ladogana A" first="Anna" last="Ladogana">Anna Ladogana</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma</wicri:regionArea></affiliation></author><author><name sortKey="Boyd, Alison" sort="Boyd, Alison" uniqKey="Boyd A" first="Alison" last="Boyd">Alison Boyd</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Victoria" sort="Lewis, Victoria" uniqKey="Lewis V" first="Victoria" last="Lewis">Victoria Lewis</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Ponto, Claudia" sort="Ponto, Claudia" uniqKey="Ponto C" first="Claudia" last="Ponto">Claudia Ponto</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen</wicri:regionArea></affiliation></author><author><name sortKey="Calero, Olga" sort="Calero, Olga" uniqKey="Calero O" first="Olga" last="Calero">Olga Calero</name><affiliation><nlm:affiliation>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</nlm:affiliation><wicri:noCountry code="no comma">Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</wicri:noCountry></affiliation></author><author><name sortKey="Poleggi, Anna" sort="Poleggi, Anna" uniqKey="Poleggi A" first="Anna" last="Poleggi">Anna Poleggi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma</wicri:regionArea></affiliation></author><author><name sortKey="Carracedo, Angel" sort="Carracedo, Angel" uniqKey="Carracedo A" first="Ángel" last="Carracedo">Ángel Carracedo</name><affiliation><nlm:affiliation>Fundación Pública Galega de Medicina Xenómica, CIBERER, Grupo de Medicina Xenómica-Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation></author><author><name sortKey="Van Der Lee, Sven J" sort="Van Der Lee, Sven J" uniqKey="Van Der Lee S" first="Sven J" last="Van Der Lee">Sven J. Van Der Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Strobel, Thomas" sort="Strobel, Thomas" uniqKey="Strobel T" first="Thomas" last="Ströbel">Thomas Ströbel</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Neurology, Medical University Vienna, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Haik, Stephane" sort="Haik, Stephane" uniqKey="Haik S" first="Stéphane" last="Haïk">Stéphane Haïk</name><affiliation wicri:level="1"><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><affiliation wicri:level="1"><nlm:affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander</wicri:regionArea></affiliation></author><author><name sortKey="Berciano, Jose" sort="Berciano, Jose" uniqKey="Berciano J" first="José" last="Berciano">José Berciano</name><affiliation wicri:level="1"><nlm:affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander</wicri:regionArea></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G" last="Uitterlinden">Andre G. Uitterlinden</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Collins, Steven J" sort="Collins, Steven J" uniqKey="Collins S" first="Steven J" last="Collins">Steven J. Collins</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Budka, Herbert" sort="Budka, Herbert" uniqKey="Budka H" first="Herbert" last="Budka">Herbert Budka</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Neurology, Medical University Vienna, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Brandel, Jean Philippe" sort="Brandel, Jean Philippe" uniqKey="Brandel J" first="Jean-Philippe" last="Brandel">Jean-Philippe Brandel</name><affiliation wicri:level="1"><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Laplanche, Jean Louis" sort="Laplanche, Jean Louis" uniqKey="Laplanche J" first="Jean Louis" last="Laplanche">Jean Louis Laplanche</name><affiliation wicri:level="1"><nlm:affiliation>Service de biochimie et biologie moleculaire, Laboratoire associé au CNR "ATNC", Hôpital Lariboisiére, AP-HP, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de biochimie et biologie moleculaire, Laboratoire associé au CNR "ATNC", Hôpital Lariboisiére, AP-HP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Pocchiari, Maurizio" sort="Pocchiari, Maurizio" uniqKey="Pocchiari M" first="Maurizio" last="Pocchiari">Maurizio Pocchiari</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma</wicri:regionArea></affiliation></author><author><name sortKey="Zerr, Inga" sort="Zerr, Inga" uniqKey="Zerr I" first="Inga" last="Zerr">Inga Zerr</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen</wicri:regionArea></affiliation></author><author><name sortKey="Knight, Richard S G" sort="Knight, Richard S G" uniqKey="Knight R" first="Richard S G" last="Knight">Richard S G. Knight</name><affiliation wicri:level="1"><nlm:affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Will, Robert G" sort="Will, Robert G" uniqKey="Will R" first="Robert G" last="Will">Robert G. Will</name><affiliation wicri:level="1"><nlm:affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25918841</idno><idno type="pmid">25918841</idno><idno type="doi">10.1371/journal.pone.0123654</idno><idno type="wicri:Area/PubMed/Corpus">002E26</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002E26</idno><idno type="wicri:Area/PubMed/Curation">002D50</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002D50</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.</title><author><name sortKey="Sanchez Juan, Pascual" sort="Sanchez Juan, Pascual" uniqKey="Sanchez Juan P" first="Pascual" last="Sanchez-Juan">Pascual Sanchez-Juan</name><affiliation wicri:level="1"><nlm:affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander</wicri:regionArea></affiliation></author><author><name sortKey="Bishop, Matthew T" sort="Bishop, Matthew T" uniqKey="Bishop M" first="Matthew T" last="Bishop">Matthew T. Bishop</name><affiliation wicri:level="1"><nlm:affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Kovacs, Gabor G" sort="Kovacs, Gabor G" uniqKey="Kovacs G" first="Gabor G" last="Kovacs">Gabor G. Kovacs</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Neurology, Medical University Vienna, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Calero, Miguel" sort="Calero, Miguel" uniqKey="Calero M" first="Miguel" last="Calero">Miguel Calero</name><affiliation wicri:level="1"><nlm:affiliation>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain; Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain; Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Aulchenko, Yurii S" sort="Aulchenko, Yurii S" uniqKey="Aulchenko Y" first="Yurii S" last="Aulchenko">Yurii S. Aulchenko</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk</wicri:regionArea></affiliation></author><author><name sortKey="Ladogana, Anna" sort="Ladogana, Anna" uniqKey="Ladogana A" first="Anna" last="Ladogana">Anna Ladogana</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma</wicri:regionArea></affiliation></author><author><name sortKey="Boyd, Alison" sort="Boyd, Alison" uniqKey="Boyd A" first="Alison" last="Boyd">Alison Boyd</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Victoria" sort="Lewis, Victoria" uniqKey="Lewis V" first="Victoria" last="Lewis">Victoria Lewis</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Ponto, Claudia" sort="Ponto, Claudia" uniqKey="Ponto C" first="Claudia" last="Ponto">Claudia Ponto</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen</wicri:regionArea></affiliation></author><author><name sortKey="Calero, Olga" sort="Calero, Olga" uniqKey="Calero O" first="Olga" last="Calero">Olga Calero</name><affiliation><nlm:affiliation>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</nlm:affiliation><wicri:noCountry code="no comma">Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</wicri:noCountry></affiliation></author><author><name sortKey="Poleggi, Anna" sort="Poleggi, Anna" uniqKey="Poleggi A" first="Anna" last="Poleggi">Anna Poleggi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma</wicri:regionArea></affiliation></author><author><name sortKey="Carracedo, Angel" sort="Carracedo, Angel" uniqKey="Carracedo A" first="Ángel" last="Carracedo">Ángel Carracedo</name><affiliation><nlm:affiliation>Fundación Pública Galega de Medicina Xenómica, CIBERER, Grupo de Medicina Xenómica-Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation></author><author><name sortKey="Van Der Lee, Sven J" sort="Van Der Lee, Sven J" uniqKey="Van Der Lee S" first="Sven J" last="Van Der Lee">Sven J. Van Der Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Strobel, Thomas" sort="Strobel, Thomas" uniqKey="Strobel T" first="Thomas" last="Ströbel">Thomas Ströbel</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Neurology, Medical University Vienna, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Haik, Stephane" sort="Haik, Stephane" uniqKey="Haik S" first="Stéphane" last="Haïk">Stéphane Haïk</name><affiliation wicri:level="1"><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><affiliation wicri:level="1"><nlm:affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander</wicri:regionArea></affiliation></author><author><name sortKey="Berciano, Jose" sort="Berciano, Jose" uniqKey="Berciano J" first="José" last="Berciano">José Berciano</name><affiliation wicri:level="1"><nlm:affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander</wicri:regionArea></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G" last="Uitterlinden">Andre G. Uitterlinden</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Collins, Steven J" sort="Collins, Steven J" uniqKey="Collins S" first="Steven J" last="Collins">Steven J. Collins</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville, 3010</wicri:regionArea></affiliation></author><author><name sortKey="Budka, Herbert" sort="Budka, Herbert" uniqKey="Budka H" first="Herbert" last="Budka">Herbert Budka</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Neurology, Medical University Vienna, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Brandel, Jean Philippe" sort="Brandel, Jean Philippe" uniqKey="Brandel J" first="Jean-Philippe" last="Brandel">Jean-Philippe Brandel</name><affiliation wicri:level="1"><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Laplanche, Jean Louis" sort="Laplanche, Jean Louis" uniqKey="Laplanche J" first="Jean Louis" last="Laplanche">Jean Louis Laplanche</name><affiliation wicri:level="1"><nlm:affiliation>Service de biochimie et biologie moleculaire, Laboratoire associé au CNR "ATNC", Hôpital Lariboisiére, AP-HP, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de biochimie et biologie moleculaire, Laboratoire associé au CNR "ATNC", Hôpital Lariboisiére, AP-HP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Pocchiari, Maurizio" sort="Pocchiari, Maurizio" uniqKey="Pocchiari M" first="Maurizio" last="Pocchiari">Maurizio Pocchiari</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma</wicri:regionArea></affiliation></author><author><name sortKey="Zerr, Inga" sort="Zerr, Inga" uniqKey="Zerr I" first="Inga" last="Zerr">Inga Zerr</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen</wicri:regionArea></affiliation></author><author><name sortKey="Knight, Richard S G" sort="Knight, Richard S G" uniqKey="Knight R" first="Richard S G" last="Knight">Richard S G. Knight</name><affiliation wicri:level="1"><nlm:affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Will, Robert G" sort="Will, Robert G" uniqKey="Will R" first="Robert G" last="Will">Robert G. Will</name><affiliation wicri:level="1"><nlm:affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Centre, Rotterdam</wicri:regionArea></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Case-Control Studies</term><term>Creutzfeldt-Jakob Syndrome (genetics)</term><term>Genome-Wide Association Study (methods)</term><term>Germany</term><term>Humans</term><term>Netherlands</term><term>Polymorphism, Single Nucleotide</term><term>Prion Proteins</term><term>Prions (genetics)</term><term>Receptors, Metabotropic Glutamate (genetics)</term><term>Signal Transduction</term><term>United Kingdom</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allemagne</term><term>Humains</term><term>Maladie de Creutzfeldt-Jakob (génétique)</term><term>Pays-Bas</term><term>Polymorphisme de nucléotide simple</term><term>Prions (génétique)</term><term>Protéines prion</term><term>Royaume-Uni</term><term>Récepteurs métabotropes au glutamate (génétique)</term><term>Transduction du signal</term><term>Étude d'association pangénomique ()</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Prions</term><term>Receptors, Metabotropic Glutamate</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Prion Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Creutzfeldt-Jakob Syndrome</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Maladie de Creutzfeldt-Jakob</term><term>Prions</term><term>Récepteurs métabotropes au glutamate</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genome-Wide Association Study</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Case-Control Studies</term><term>Germany</term><term>Humans</term><term>Netherlands</term><term>Polymorphism, Single Nucleotide</term><term>Signal Transduction</term><term>United Kingdom</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Allemagne</term><term>Humains</term><term>Pays-Bas</term><term>Polymorphisme de nucléotide simple</term><term>Protéines prion</term><term>Royaume-Uni</term><term>Transduction du signal</term><term>Étude d'association pangénomique</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25918841</PMID><DateCreated><Year>2015</Year><Month>04</Month><Day>29</Day></DateCreated><DateCompleted><Year>2016</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>4</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.</ArticleTitle><Pagination><MedlinePgn>e0123654</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0123654</ELocationID><Abstract><AbstractText>We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sanchez-Juan</LastName><ForeName>Pascual</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bishop</LastName><ForeName>Matthew T</ForeName><Initials>MT</Initials><AffiliationInfo><Affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kovacs</LastName><ForeName>Gabor G</ForeName><Initials>GG</Initials><AffiliationInfo><Affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Calero</LastName><ForeName>Miguel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain; Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aulchenko</LastName><ForeName>Yurii S</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ladogana</LastName><ForeName>Anna</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyd</LastName><ForeName>Alison</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewis</LastName><ForeName>Victoria</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ponto</LastName><ForeName>Claudia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Calero</LastName><ForeName>Olga</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Chronic Disease Programme and CIBERNED. Carlos III Institute of Health. Madrid. Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poleggi</LastName><ForeName>Anna</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carracedo</LastName><ForeName>Ángel</ForeName><Initials>Á</Initials><AffiliationInfo><Affiliation>Fundación Pública Galega de Medicina Xenómica, CIBERER, Grupo de Medicina Xenómica-Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, KSA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van der Lee</LastName><ForeName>Sven J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ströbel</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rivadeneira</LastName><ForeName>Fernando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hofman</LastName><ForeName>Albert</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haïk</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Combarros</LastName><ForeName>Onofre</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Berciano</LastName><ForeName>José</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Neurology Department, University Hospital "Marqués de Valdecilla". Instituto de Investigación "Marqués de Valdecilla" IDIVAL and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Santander, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uitterlinden</LastName><ForeName>Andre G</ForeName><Initials>AG</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Collins</LastName><ForeName>Steven J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Department of Pathology, The University of Melbourne, Parkville, 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Budka</LastName><ForeName>Herbert</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Institute of Neurology, Medical University Vienna, Vienna, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brandel</LastName><ForeName>Jean-Philippe</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, and Inserm, U 1127, and CNRS UMR 7225, and ICM, F-75013, Paris, France; AP-HP, Hôpital de la Pitié Salpêtrière, Cellule Nationale de Référence des maladies de Creutzfeldt-Jakob, F-75013, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laplanche</LastName><ForeName>Jean Louis</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Service de biochimie et biologie moleculaire, Laboratoire associé au CNR "ATNC", Hôpital Lariboisiére, AP-HP, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pocchiari</LastName><ForeName>Maurizio</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Cell Biology and Neurosciences Instituto Superiore di Sanità, Roma, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zerr</LastName><ForeName>Inga</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Neurology, Clinical Dementia Centre, University Medical Center and German Center for Neurodegenerative Diseases (DZNE)-site Göttingen, Göttingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Knight</LastName><ForeName>Richard S G</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Will</LastName><ForeName>Robert G</ForeName><Initials>RG</Initials><AffiliationInfo><Affiliation>The National Creutzfeldt-Jakob disease Research and Surveillance Unit, University of Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Duijn</LastName><ForeName>Cornelia M</ForeName><Initials>CM</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D017418">Meta-Analysis</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>04</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C512656">PRNP protein, 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Association Study</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005858" MajorTopicYN="N">Germany</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009426" MajorTopicYN="N">Netherlands</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="Y">Polymorphism, Single Nucleotide</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000072002" MajorTopicYN="N">Prion Proteins</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011328" MajorTopicYN="N">Prions</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018094" MajorTopicYN="N">Receptors, Metabotropic Glutamate</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006113" MajorTopicYN="N">United Kingdom</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4412535</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>01</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>02</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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