Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24657781
TITLE
Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling.
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.
Copyright 2014 Elsevier Inc. All rights reserved.
DATE PUBLISHED
2014 Jul 15
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/10/05
revised 2014/02/21
accepted 2014/03/04
aheadofprint 2014/03/18
entrez 2014/03/25 06:00
pubmed 2014/03/25 06:00
medline 2015/01/13 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Kochunov P Kochunov Peter P Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: pkochunov@mprc.umaryland.edu.
Jahanshad N Jahanshad Neda N Imaging Genetics Center, Institute of Neuroimaging and Informatics, Department of Neurology, Keck School of Medicine of USC, Los Angeles, CA, USA.
Sprooten E Sprooten Emma E Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA.
Nichols TE Nichols Thomas E TE Department of Statistics & Warwick Manufacturing Group, The University of Warwick, Coventry, UK; Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
Mandl RC Mandl René C RC Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Almasy L Almasy Laura L Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
Booth T Booth Tom T Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Brouwer RM Brouwer Rachel M RM Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Curran JE Curran Joanne E JE Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
de Zubicaray GI de Zubicaray Greig I GI School of Psychology, University of Queensland, Brisbane, Australia.
Dimitrova R Dimitrova Rali R Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Duggirala R Duggirala Ravi R Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
Fox PT Fox Peter T PT Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Hong LE Hong L Elliot LE Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Landman BA Landman Bennett A BA Department of Electrical Engineering, Vanderbilt University, Nashville, TN, USA.
Lemaitre H Lemaitre Hervé H U1000 Research Unit Neuroimaging and Psychiatry, INSERM-CEA-Faculté de Médecine Paris-Sud, Orsay, France.
Lopez LM Lopez Lorna M LM Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
McMahon KL McMahon Katie L KL Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
Mitchell BD Mitchell Braxton D BD Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Olvera RL Olvera Rene L RL Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Peterson CP Peterson Charles P CP Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
Starr JM Starr John M JM Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
Sussmann JE Sussmann Jessika E JE Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Toga AW Toga Arthur W AW Imaging Genetics Center, Institute of Neuroimaging and Informatics, Department of Neurology, Keck School of Medicine of USC, Los Angeles, CA, USA.
Wardlaw JM Wardlaw Joanna M JM Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK; Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh, UK.
Wright MJ Wright Margaret J MJ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Wright SN Wright Susan N SN Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Bastin ME Bastin Mark E ME Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK; Brain Research Imaging Centre, Centre for Clinical Brain Sciences, University of Edinburgh, UK.
McIntosh AM McIntosh Andrew M AM Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Kahn RS Kahn René S RS Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
den Braber A den Braber Anouk A Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
de Geus EJ de Geus Eco J C EJ Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Hulshoff Pol HE Hulshoff Pol Hilleke E HE Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Williamson DE Williamson Douglas E DE Department of Psychiatry, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Blangero J Blangero John J Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
van 't Ent D van 't Ent Dennis D Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Thompson PM Thompson Paul M PM Imaging Genetics Center, Institute of Neuroimaging and Informatics, Department of Neurology, Keck School of Medicine of USC, Los Angeles, CA, USA; Department of Neurology, Pediatrics, Engineering, Psychiatry, Radiology, & Ophthalmology, University of Southern California, Los Angeles, CA, USA.
Glahn DC Glahn David C DC Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA.
INVESTIGATORS
JOURNAL
VOLUME: 95
ISSUE:
TITLE: NeuroImage
ISOABBREVIATION: Neuroimage
YEAR: 2014
MONTH: Jul
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1095-9572
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Neuroimage
COUNTRY: United States
ISSNLINKING: 1053-8119
NLMUNIQUEID: 9215515
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
087727/Z/08/Z Wellcome Trust United Kingdom
100309 Wellcome Trust United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
EB007813 NIBIB NIH HHS United States
EB008281 NIBIB NIH HHS United States
EB008432 NIBIB NIH HHS United States
G0700704 Medical Research Council United Kingdom
G0701120 Medical Research Council United Kingdom
G1001245 Medical Research Council United Kingdom
MH0708143 NIMH NIH HHS United States
MH083824 NIMH NIH HHS United States
MH59490 NIMH NIH HHS United States
MR/K026992/1 Medical Research Council United Kingdom
P41 EB015922 NIBIB NIH HHS United States
R01 EB015611 NIBIB NIH HHS United States
R01 EB015611 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01AA016274 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Diffusion tensor imaging (DTI)
Heritability
Imaging genetics
Meta-analysis
Multi-site
Reliability
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Anisotropy
Brain
Child
Diffusion Tensor Imaging
Female
Genetic Variation
Humans
Male
Meta-Analysis as Topic
Middle Aged
White Matter
Young Adult
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS578312 NLM
PMC4043878 NLM