Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and mega analytical approaches for data pooling
Identifieur interne : 002121 ( Pmc/Corpus ); précédent : 002120; suivant : 002122Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and mega analytical approaches for data pooling
Auteurs : Peter Kochunov ; Neda Jahanshad ; Emma Sprooten ; Thomas E. Nichols ; René C. Mandl ; Laura Almasy ; Tom Booth ; Rachel M. Brouwer ; Joanne E. Curran ; Greig I. De Zubicaray ; Rali Dimitrova ; Ravi Duggirala ; Peter T. Fox ; L. Elliot Hong ; Bennett A. Landman ; Hervé Lemaitre ; Lorna Lopez ; Nicholas G. Martin ; Katie L. Mcmahon ; Braxton D. Mitchell ; Rene L. Olvera ; Charles P. Peterson ; John M. Starr ; Jessika E. Sussmann ; Arthur W. Toga ; Joanna M. Wardlaw ; Margaret J. Wright ; Susan N. Wright ; Mark E. Bastin ; Andrew M. Mcintosh ; Dorret I. Boomsma ; René S. Kahn ; Anouk Den Braber ; Eco Jc De Geus ; Ian J. Deary ; Hilleke E. Hulshoff Pol ; Douglas E. Williamson ; John Blangero ; Dennis Van Ent ; Paul M. Thompson ; David C. GlahnSource :
- NeuroImage [ 1053-8119 ] ; 2014.
Abstract
Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9–85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large “mega-family”. We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.
Url:
DOI: 10.1016/j.neuroimage.2014.03.033
PubMed: 24657781
PubMed Central: 4043878
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PMC:4043878Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and mega analytical approaches for data pooling</title><author><name sortKey="Kochunov, Peter" sort="Kochunov, Peter" uniqKey="Kochunov P" first="Peter" last="Kochunov">Peter Kochunov</name><affiliation><nlm:aff id="A1">Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Jahanshad, Neda" sort="Jahanshad, Neda" uniqKey="Jahanshad N" first="Neda" last="Jahanshad">Neda Jahanshad</name><affiliation><nlm:aff id="A2">Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Sprooten, Emma" sort="Sprooten, Emma" uniqKey="Sprooten E" first="Emma" last="Sprooten">Emma Sprooten</name><affiliation><nlm:aff id="A3">Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA</nlm:aff></affiliation></author><author><name sortKey="Nichols, Thomas E" sort="Nichols, Thomas E" uniqKey="Nichols T" first="Thomas E." last="Nichols">Thomas E. Nichols</name><affiliation><nlm:aff id="A4">Department of Statistics & Warwick Manufacturing Group, The University of Warwick, Coventry, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Oxford University, UK</nlm:aff></affiliation></author><author><name sortKey="Mandl, Rene C" sort="Mandl, Rene C" uniqKey="Mandl R" first="René C." last="Mandl">René C. Mandl</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Almasy, Laura" sort="Almasy, Laura" uniqKey="Almasy L" first="Laura" last="Almasy">Laura Almasy</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Booth, Tom" sort="Booth, Tom" uniqKey="Booth T" first="Tom" last="Booth">Tom Booth</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Brouwer, Rachel M" sort="Brouwer, Rachel M" uniqKey="Brouwer R" first="Rachel M." last="Brouwer">Rachel M. Brouwer</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Curran, Joanne E" sort="Curran, Joanne E" uniqKey="Curran J" first="Joanne E." last="Curran">Joanne E. Curran</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="De Zubicaray, Greig I" sort="De Zubicaray, Greig I" uniqKey="De Zubicaray G" first="Greig I." last="De Zubicaray">Greig I. De Zubicaray</name><affiliation><nlm:aff id="A9">School of Psychology, University of Queensland, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Dimitrova, Rali" sort="Dimitrova, Rali" uniqKey="Dimitrova R" first="Rali" last="Dimitrova">Rali Dimitrova</name><affiliation><nlm:aff id="A10">Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Duggirala, Ravi" sort="Duggirala, Ravi" uniqKey="Duggirala R" first="Ravi" last="Duggirala">Ravi Duggirala</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Fox, Peter T" sort="Fox, Peter T" uniqKey="Fox P" first="Peter T." last="Fox">Peter T. Fox</name><affiliation><nlm:aff id="A11">Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Hong, L Elliot" sort="Hong, L Elliot" uniqKey="Hong L" first="L. Elliot" last="Hong">L. Elliot Hong</name><affiliation><nlm:aff id="A1">Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Landman, Bennett A" sort="Landman, Bennett A" uniqKey="Landman B" first="Bennett A." last="Landman">Bennett A. Landman</name><affiliation><nlm:aff id="A12">Department of Electrical Engineering, Vanderbilt University, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Lemaitre, Herve" sort="Lemaitre, Herve" uniqKey="Lemaitre H" first="Hervé" last="Lemaitre">Hervé Lemaitre</name><affiliation><nlm:aff id="A13">U1000 Research Unit Neuroimaging and Psychiatry, INSERM-CEA-Faculté de Médecine Paris-Sud. Orsay, France</nlm:aff></affiliation></author><author><name sortKey="Lopez, Lorna" sort="Lopez, Lorna" uniqKey="Lopez L" first="Lorna" last="Lopez">Lorna Lopez</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A15">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcmahon, Katie L" sort="Mcmahon, Katie L" uniqKey="Mcmahon K" first="Katie L." last="Mcmahon">Katie L. Mcmahon</name><affiliation><nlm:aff id="A16">Center for Advanced Imaging, University of Queensland, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D." last="Mitchell">Braxton D. Mitchell</name><affiliation><nlm:aff id="A17">Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Olvera, Rene L" sort="Olvera, Rene L" uniqKey="Olvera R" first="Rene L." last="Olvera">Rene L. Olvera</name><affiliation><nlm:aff id="A18">Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Peterson, Charles P" sort="Peterson, Charles P" uniqKey="Peterson C" first="Charles P." last="Peterson">Charles P. Peterson</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M." last="Starr">John M. Starr</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Sussmann, Jessika E" sort="Sussmann, Jessika E" uniqKey="Sussmann J" first="Jessika E." last="Sussmann">Jessika E. Sussmann</name><affiliation><nlm:aff id="A10">Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Toga, Arthur W" sort="Toga, Arthur W" uniqKey="Toga A" first="Arthur W." last="Toga">Arthur W. Toga</name><affiliation><nlm:aff id="A2">Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Wardlaw, Joanna M" sort="Wardlaw, Joanna M" uniqKey="Wardlaw J" first="Joanna M." last="Wardlaw">Joanna M. Wardlaw</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh</nlm:aff></affiliation></author><author><name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name><affiliation><nlm:aff id="A15">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Wright, Susan N" sort="Wright, Susan N" uniqKey="Wright S" first="Susan N." last="Wright">Susan N. Wright</name><affiliation><nlm:aff id="A1">Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Bastin, Mark E" sort="Bastin, Mark E" uniqKey="Bastin M" first="Mark E." last="Bastin">Mark E. Bastin</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh</nlm:aff></affiliation></author><author><name sortKey="Mcintosh, Andrew M" sort="Mcintosh, Andrew M" uniqKey="Mcintosh A" first="Andrew M." last="Mcintosh">Andrew M. Mcintosh</name><affiliation><nlm:aff id="A10">Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Boomsma, Dorret I" sort="Boomsma, Dorret I" uniqKey="Boomsma D" first="Dorret I." last="Boomsma">Dorret I. Boomsma</name><affiliation><nlm:aff id="A20">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kahn, Rene S" sort="Kahn, Rene S" uniqKey="Kahn R" first="René S." last="Kahn">René S. Kahn</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Den Braber, Anouk" sort="Den Braber, Anouk" uniqKey="Den Braber A" first="Anouk" last="Den Braber">Anouk Den Braber</name><affiliation><nlm:aff id="A20">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Geus, Eco Jc" sort="De Geus, Eco Jc" uniqKey="De Geus E" first="Eco Jc" last="De Geus">Eco Jc De Geus</name><affiliation><nlm:aff id="A20">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J." last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hulshoff Pol, Hilleke E" sort="Hulshoff Pol, Hilleke E" uniqKey="Hulshoff Pol H" first="Hilleke E." last="Hulshoff Pol">Hilleke E. Hulshoff Pol</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williamson, Douglas E" sort="Williamson, Douglas E" uniqKey="Williamson D" first="Douglas E." last="Williamson">Douglas E. Williamson</name><affiliation><nlm:aff id="A18">Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Van Ent, Dennis" sort="Van Ent, Dennis" uniqKey="Van Ent D" first="Dennis" last="Van Ent">Dennis Van Ent</name></author><author><name sortKey="Thompson, Paul M" sort="Thompson, Paul M" uniqKey="Thompson P" first="Paul M." last="Thompson">Paul M. Thompson</name><affiliation><nlm:aff id="A2">Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Glahn, David C" sort="Glahn, David C" uniqKey="Glahn D" first="David C." last="Glahn">David C. Glahn</name><affiliation><nlm:aff id="A3">Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24657781</idno><idno type="pmc">4043878</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043878</idno><idno type="RBID">PMC:4043878</idno><idno type="doi">10.1016/j.neuroimage.2014.03.033</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002121</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002121</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and mega analytical approaches for data pooling</title><author><name sortKey="Kochunov, Peter" sort="Kochunov, Peter" uniqKey="Kochunov P" first="Peter" last="Kochunov">Peter Kochunov</name><affiliation><nlm:aff id="A1">Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Jahanshad, Neda" sort="Jahanshad, Neda" uniqKey="Jahanshad N" first="Neda" last="Jahanshad">Neda Jahanshad</name><affiliation><nlm:aff id="A2">Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Sprooten, Emma" sort="Sprooten, Emma" uniqKey="Sprooten E" first="Emma" last="Sprooten">Emma Sprooten</name><affiliation><nlm:aff id="A3">Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA</nlm:aff></affiliation></author><author><name sortKey="Nichols, Thomas E" sort="Nichols, Thomas E" uniqKey="Nichols T" first="Thomas E." last="Nichols">Thomas E. Nichols</name><affiliation><nlm:aff id="A4">Department of Statistics & Warwick Manufacturing Group, The University of Warwick, Coventry, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Oxford University, UK</nlm:aff></affiliation></author><author><name sortKey="Mandl, Rene C" sort="Mandl, Rene C" uniqKey="Mandl R" first="René C." last="Mandl">René C. Mandl</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Almasy, Laura" sort="Almasy, Laura" uniqKey="Almasy L" first="Laura" last="Almasy">Laura Almasy</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Booth, Tom" sort="Booth, Tom" uniqKey="Booth T" first="Tom" last="Booth">Tom Booth</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Brouwer, Rachel M" sort="Brouwer, Rachel M" uniqKey="Brouwer R" first="Rachel M." last="Brouwer">Rachel M. Brouwer</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Curran, Joanne E" sort="Curran, Joanne E" uniqKey="Curran J" first="Joanne E." last="Curran">Joanne E. Curran</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="De Zubicaray, Greig I" sort="De Zubicaray, Greig I" uniqKey="De Zubicaray G" first="Greig I." last="De Zubicaray">Greig I. De Zubicaray</name><affiliation><nlm:aff id="A9">School of Psychology, University of Queensland, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Dimitrova, Rali" sort="Dimitrova, Rali" uniqKey="Dimitrova R" first="Rali" last="Dimitrova">Rali Dimitrova</name><affiliation><nlm:aff id="A10">Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Duggirala, Ravi" sort="Duggirala, Ravi" uniqKey="Duggirala R" first="Ravi" last="Duggirala">Ravi Duggirala</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Fox, Peter T" sort="Fox, Peter T" uniqKey="Fox P" first="Peter T." last="Fox">Peter T. Fox</name><affiliation><nlm:aff id="A11">Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Hong, L Elliot" sort="Hong, L Elliot" uniqKey="Hong L" first="L. Elliot" last="Hong">L. Elliot Hong</name><affiliation><nlm:aff id="A1">Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Landman, Bennett A" sort="Landman, Bennett A" uniqKey="Landman B" first="Bennett A." last="Landman">Bennett A. Landman</name><affiliation><nlm:aff id="A12">Department of Electrical Engineering, Vanderbilt University, Nashville, TN, USA</nlm:aff></affiliation></author><author><name sortKey="Lemaitre, Herve" sort="Lemaitre, Herve" uniqKey="Lemaitre H" first="Hervé" last="Lemaitre">Hervé Lemaitre</name><affiliation><nlm:aff id="A13">U1000 Research Unit Neuroimaging and Psychiatry, INSERM-CEA-Faculté de Médecine Paris-Sud. Orsay, France</nlm:aff></affiliation></author><author><name sortKey="Lopez, Lorna" sort="Lopez, Lorna" uniqKey="Lopez L" first="Lorna" last="Lopez">Lorna Lopez</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A15">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcmahon, Katie L" sort="Mcmahon, Katie L" uniqKey="Mcmahon K" first="Katie L." last="Mcmahon">Katie L. Mcmahon</name><affiliation><nlm:aff id="A16">Center for Advanced Imaging, University of Queensland, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Mitchell, Braxton D" sort="Mitchell, Braxton D" uniqKey="Mitchell B" first="Braxton D." last="Mitchell">Braxton D. Mitchell</name><affiliation><nlm:aff id="A17">Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Olvera, Rene L" sort="Olvera, Rene L" uniqKey="Olvera R" first="Rene L." last="Olvera">Rene L. Olvera</name><affiliation><nlm:aff id="A18">Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Peterson, Charles P" sort="Peterson, Charles P" uniqKey="Peterson C" first="Charles P." last="Peterson">Charles P. Peterson</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M." last="Starr">John M. Starr</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Sussmann, Jessika E" sort="Sussmann, Jessika E" uniqKey="Sussmann J" first="Jessika E." last="Sussmann">Jessika E. Sussmann</name><affiliation><nlm:aff id="A10">Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Toga, Arthur W" sort="Toga, Arthur W" uniqKey="Toga A" first="Arthur W." last="Toga">Arthur W. Toga</name><affiliation><nlm:aff id="A2">Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Wardlaw, Joanna M" sort="Wardlaw, Joanna M" uniqKey="Wardlaw J" first="Joanna M." last="Wardlaw">Joanna M. Wardlaw</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh</nlm:aff></affiliation></author><author><name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name><affiliation><nlm:aff id="A15">QIMR Berghofer Medical Research Institute, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Wright, Susan N" sort="Wright, Susan N" uniqKey="Wright S" first="Susan N." last="Wright">Susan N. Wright</name><affiliation><nlm:aff id="A1">Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Bastin, Mark E" sort="Bastin, Mark E" uniqKey="Bastin M" first="Mark E." last="Bastin">Mark E. Bastin</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh</nlm:aff></affiliation></author><author><name sortKey="Mcintosh, Andrew M" sort="Mcintosh, Andrew M" uniqKey="Mcintosh A" first="Andrew M." last="Mcintosh">Andrew M. Mcintosh</name><affiliation><nlm:aff id="A10">Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Boomsma, Dorret I" sort="Boomsma, Dorret I" uniqKey="Boomsma D" first="Dorret I." last="Boomsma">Dorret I. Boomsma</name><affiliation><nlm:aff id="A20">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Kahn, Rene S" sort="Kahn, Rene S" uniqKey="Kahn R" first="René S." last="Kahn">René S. Kahn</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Den Braber, Anouk" sort="Den Braber, Anouk" uniqKey="Den Braber A" first="Anouk" last="Den Braber">Anouk Den Braber</name><affiliation><nlm:aff id="A20">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Geus, Eco Jc" sort="De Geus, Eco Jc" uniqKey="De Geus E" first="Eco Jc" last="De Geus">Eco Jc De Geus</name><affiliation><nlm:aff id="A20">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J." last="Deary">Ian J. Deary</name><affiliation><nlm:aff id="A8">Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Hulshoff Pol, Hilleke E" sort="Hulshoff Pol, Hilleke E" uniqKey="Hulshoff Pol H" first="Hilleke E." last="Hulshoff Pol">Hilleke E. Hulshoff Pol</name><affiliation><nlm:aff id="A6">Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williamson, Douglas E" sort="Williamson, Douglas E" uniqKey="Williamson D" first="Douglas E." last="Williamson">Douglas E. Williamson</name><affiliation><nlm:aff id="A18">Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name><affiliation><nlm:aff id="A7">Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Van Ent, Dennis" sort="Van Ent, Dennis" uniqKey="Van Ent D" first="Dennis" last="Van Ent">Dennis Van Ent</name></author><author><name sortKey="Thompson, Paul M" sort="Thompson, Paul M" uniqKey="Thompson P" first="Paul M." last="Thompson">Paul M. Thompson</name><affiliation><nlm:aff id="A2">Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Glahn, David C" sort="Glahn, David C" uniqKey="Glahn D" first="David C." last="Glahn">David C. Glahn</name><affiliation><nlm:aff id="A3">Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA</nlm:aff></affiliation></author></analytic><series><title level="j">NeuroImage</title><idno type="ISSN">1053-8119</idno><idno type="eISSN">1095-9572</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9–85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large “mega-family”. We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9215515</journal-id><journal-id journal-id-type="pubmed-jr-id">20498</journal-id><journal-id journal-id-type="nlm-ta">Neuroimage</journal-id><journal-id journal-id-type="iso-abbrev">Neuroimage</journal-id><journal-title-group><journal-title>NeuroImage</journal-title></journal-title-group><issn pub-type="ppub">1053-8119</issn><issn pub-type="epub">1095-9572</issn></journal-meta><article-meta><article-id pub-id-type="pmid">24657781</article-id><article-id pub-id-type="pmc">4043878</article-id><article-id pub-id-type="doi">10.1016/j.neuroimage.2014.03.033</article-id><article-id pub-id-type="manuscript">NIHMS578312</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: comparing meta and mega analytical approaches for data pooling</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kochunov</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">#</xref></contrib><contrib contrib-type="author"><name><surname>Jahanshad</surname><given-names>Neda</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">#</xref></contrib><contrib contrib-type="author"><name><surname>Sprooten</surname><given-names>Emma</given-names></name><xref ref-type="aff" rid="A3">4</xref></contrib><contrib contrib-type="author"><name><surname>Nichols</surname><given-names>Thomas E.</given-names></name><xref ref-type="aff" rid="A4">5</xref><xref ref-type="aff" rid="A5">6</xref></contrib><contrib contrib-type="author"><name><surname>Mandl</surname><given-names>René C.</given-names></name><xref ref-type="aff" rid="A6">7</xref></contrib><contrib contrib-type="author"><name><surname>Almasy</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="A7">8</xref></contrib><contrib contrib-type="author"><name><surname>Booth</surname><given-names>Tom</given-names></name><xref ref-type="aff" rid="A8">9</xref></contrib><contrib contrib-type="author"><name><surname>Brouwer</surname><given-names>Rachel M.</given-names></name><xref ref-type="aff" rid="A6">7</xref></contrib><contrib contrib-type="author"><name><surname>Curran</surname><given-names>Joanne E.</given-names></name><xref ref-type="aff" rid="A7">8</xref></contrib><contrib contrib-type="author"><name><surname>de Zubicaray</surname><given-names>Greig I.</given-names></name><xref ref-type="aff" rid="A9">10</xref></contrib><contrib contrib-type="author"><name><surname>Dimitrova</surname><given-names>Rali</given-names></name><xref ref-type="aff" rid="A10">11</xref></contrib><contrib contrib-type="author"><name><surname>Duggirala</surname><given-names>Ravi</given-names></name><xref ref-type="aff" rid="A7">8</xref></contrib><contrib contrib-type="author"><name><surname>Fox</surname><given-names>Peter T.</given-names></name><xref ref-type="aff" rid="A11">12</xref></contrib><contrib contrib-type="author"><name><surname>Hong</surname><given-names>L. Elliot</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Landman</surname><given-names>Bennett A.</given-names></name><xref ref-type="aff" rid="A12">13</xref></contrib><contrib contrib-type="author"><name><surname>Lemaitre</surname><given-names>Hervé</given-names></name><xref ref-type="aff" rid="A13">14</xref></contrib><contrib contrib-type="author"><name><surname>Lopez</surname><given-names>Lorna</given-names></name><xref ref-type="aff" rid="A8">9</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Nicholas G.</given-names></name><xref ref-type="aff" rid="A15">16</xref></contrib><contrib contrib-type="author"><name><surname>McMahon</surname><given-names>Katie L.</given-names></name><xref ref-type="aff" rid="A16">17</xref></contrib><contrib contrib-type="author"><name><surname>Mitchell</surname><given-names>Braxton D.</given-names></name><xref ref-type="aff" rid="A17">18</xref></contrib><contrib contrib-type="author"><name><surname>Olvera</surname><given-names>Rene L.</given-names></name><xref ref-type="aff" rid="A18">19</xref></contrib><contrib contrib-type="author"><name><surname>Peterson</surname><given-names>Charles P.</given-names></name><xref ref-type="aff" rid="A7">8</xref></contrib><contrib contrib-type="author"><name><surname>Starr</surname><given-names>John M.</given-names></name><xref ref-type="aff" rid="A8">9</xref><xref ref-type="aff" rid="A19">20</xref></contrib><contrib contrib-type="author"><name><surname>Sussmann</surname><given-names>Jessika E.</given-names></name><xref ref-type="aff" rid="A10">11</xref></contrib><contrib contrib-type="author"><name><surname>Toga</surname><given-names>Arthur W.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wardlaw</surname><given-names>Joanna M.</given-names></name><xref ref-type="aff" rid="A8">9</xref><xref ref-type="aff" rid="A14">15</xref></contrib><contrib contrib-type="author"><name><surname>Wright</surname><given-names>Margaret J.</given-names></name><xref ref-type="aff" rid="A15">16</xref></contrib><contrib contrib-type="author"><name><surname>Wright</surname><given-names>Susan N.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bastin</surname><given-names>Mark E.</given-names></name><xref ref-type="aff" rid="A8">9</xref><xref ref-type="aff" rid="A14">15</xref></contrib><contrib contrib-type="author"><name><surname>McIntosh</surname><given-names>Andrew M.</given-names></name><xref ref-type="aff" rid="A10">11</xref></contrib><contrib contrib-type="author"><name><surname>Boomsma</surname><given-names>Dorret I.</given-names></name><xref ref-type="aff" rid="A20">21</xref></contrib><contrib contrib-type="author"><name><surname>Kahn</surname><given-names>René S.</given-names></name><xref ref-type="aff" rid="A6">7</xref></contrib><contrib contrib-type="author"><name><surname>den Braber</surname><given-names>Anouk</given-names></name><xref ref-type="aff" rid="A20">21</xref></contrib><contrib contrib-type="author"><name><surname>de Geus</surname><given-names>Eco JC</given-names></name><xref ref-type="aff" rid="A20">21</xref></contrib><contrib contrib-type="author"><name><surname>Deary</surname><given-names>Ian J.</given-names></name><xref ref-type="aff" rid="A8">9</xref></contrib><contrib contrib-type="author"><name><surname>Hulshoff Pol</surname><given-names>Hilleke E.</given-names></name><xref ref-type="aff" rid="A6">7</xref></contrib><contrib contrib-type="author"><name><surname>Williamson</surname><given-names>Douglas E.</given-names></name><xref ref-type="aff" rid="A18">19</xref></contrib><contrib contrib-type="author"><name><surname>Blangero</surname><given-names>John</given-names></name><xref ref-type="aff" rid="A7">8</xref></contrib><contrib contrib-type="author"><name><surname>van ’t Ent</surname><given-names>Dennis</given-names></name></contrib><contrib contrib-type="author"><name><surname>Thompson</surname><given-names>Paul M.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Glahn</surname><given-names>David C.</given-names></name><xref ref-type="aff" rid="A3">4</xref></contrib></contrib-group><aff id="A1"><label>1</label>Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA</aff><aff id="A2"><label>2</label>Imaging Genetics Center, Institute of Neuroimaging Informatics, USC Keck School of Medicine, Los Angeles, CA, USA</aff><aff id="A3"><label>4</label>Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA</aff><aff id="A4"><label>5</label>Department of Statistics & Warwick Manufacturing Group, The University of Warwick, Coventry, UK</aff><aff id="A5"><label>6</label>Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Oxford University, UK</aff><aff id="A6"><label>7</label>Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands</aff><aff id="A7"><label>8</label>Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA</aff><aff id="A8"><label>9</label>Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK</aff><aff id="A9"><label>10</label>School of Psychology, University of Queensland, Brisbane, Australia</aff><aff id="A10"><label>11</label>Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK</aff><aff id="A11"><label>12</label>Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</aff><aff id="A12"><label>13</label>Department of Electrical Engineering, Vanderbilt University, Nashville, TN, USA</aff><aff id="A13"><label>14</label>U1000 Research Unit Neuroimaging and Psychiatry, INSERM-CEA-Faculté de Médecine Paris-Sud. Orsay, France</aff><aff id="A14"><label>15</label>Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh</aff><aff id="A15"><label>16</label>QIMR Berghofer Medical Research Institute, Brisbane, Australia</aff><aff id="A16"><label>17</label>Center for Advanced Imaging, University of Queensland, Brisbane, Australia</aff><aff id="A17"><label>18</label>Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA</aff><aff id="A18"><label>19</label>Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA</aff><aff id="A19"><label>20</label>Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK</aff><aff id="A20"><label>21</label>Department of Biological Psychology, VU University, Amsterdam, The Netherlands</aff><author-notes><corresp id="FN1"><label>*</label>Please address correspondence to: Dr. Peter Kochunov, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, School of Medicine, Baltimore, MD, USA, Phone: (410) 402-6110, <email>pkochunov@mprc.umaryland.edu</email></corresp><fn id="FN2" fn-type="equal"><label>#</label><p>PK and NJ contributed equally to this work</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>1</day><month>5</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>18</day><month>3</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>7</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>7</month><year>2015</year></pub-date><volume>95</volume><fpage>136</fpage><lpage>150</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.neuroimage.2014.03.033</pmc-comment>
<permissions><copyright-statement>© 2014 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p id="P2">Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9–85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large “mega-family”. We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.</p></abstract><kwd-group><kwd>Diffusion Tensor Imaging (DTI)</kwd><kwd>Imaging Genetics</kwd><kwd>Heritability</kwd><kwd>Meta-analysis</kwd><kwd>Multi-site</kwd><kwd>Reliability</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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