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
29051922
TITLE
Hidden heritability due to heterogeneity across seven populations.
ABSTRACT
Meta-analyses of genome-wide association studies (GWAS), which dominate genetic discovery are based on data from diverse historical time periods and populations. Genetic scores derived from GWAS explain only a fraction of the heritability estimates obtained from whole-genome studies on single populations, known as the 'hidden heritability' puzzle. Using seven sampling populations (N=35,062), we test whether hidden heritability is attributed to heterogeneity across sampling populations and time, showing that estimates are substantially smaller from across compared to within populations. We show that the hidden heritability varies substantially: from zero (height), to 20% for BMI, 37% for education, 40% for age at first birth and up to 75% for number of children. Simulations demonstrate that our results more likely reflect heterogeneity in phenotypic measurement or gene-environment interaction than genetic heterogeneity. These findings have substantial implications for genetic discovery, suggesting that large homogenous datasets are required for behavioural phenotypes and that gene-environment interaction may be a central challenge for genetic discovery.
DATE PUBLISHED
2017 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
pmc-release 2018/04/01
entrez 2017/10/21 06:00
pubmed 2017/10/21 06:00
medline 2017/10/21 06:01
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Tropf FC Tropf Felix C FC Department of Sociology/ Nuffield College, University of Oxford, Oxford OX1 3UQ, UK.
Lee SH Lee S Hong SH School of Environmental and Rural Science, The University of New England, Armidale NSW 2351, Australia.
Verweij RM Verweij Renske M RM Department of Sociology/Interuniversity Center for Social Science Theory and Methodology, University of Groningen, Groningen 9712 TG, The Netherlands.
Stulp G Stulp Gert G Department of Sociology/Interuniversity Center for Social Science Theory and Methodology, University of Groningen, Groningen 9712 TG, The Netherlands.
van der Most PJ van der Most Peter J PJ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, Netherlands.
de Vlaming R de Vlaming Ronald R Department of Complex Trait Genetics, VU University Amsterdam, Amsterdam, the Netherlands.
Bakshi A Bakshi Andrew A Institute of Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
Briley DA Briley Daniel A DA Department of Psychology, University of Illinois at Urbana-Champaign, Champaign 61820-9998, USA.
Rahal C Rahal Charles C Department of Sociology/ Nuffield College, University of Oxford, Oxford OX1 3UQ, UK.
Hellpap R Hellpap Robert R Department of Sociology/ Nuffield College, University of Oxford, Oxford OX1 3UQ, UK.
Nyman A Nyman Anastasia A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, Stockholm SE-171 77, Sweden.
Esko T Esko Tõnu T Estonian Genome Center, University of Tartu, Tartu, Estonia, 51010.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia, 51010.
Medland SE Medland Sarah E SE Quantitative Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Martin NG Martin Nicholas G NG Quantitative Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Barban N Barban Nicola N Department of Sociology/ Nuffield College, University of Oxford, Oxford OX1 3UQ, UK.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen 9700 RB, Netherlands.
Robinson MR Robinson Matthew R MR Department of Computational Biology, University of Lausanne, Lausanne, CH-1015, Switzerland.
Mills MC Mills Melinda C MC Department of Sociology/ Nuffield College, University of Oxford, Oxford OX1 3UQ, UK.
INVESTIGATORS
JOURNAL
VOLUME: 1
ISSUE: 10
TITLE: Nature human behaviour
ISOABBREVIATION: Nat Hum Behav
YEAR: 2017
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 2397-3374
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Nat Hum Behav
COUNTRY: England
ISSNLINKING:
NLMUNIQUEID: 101697750
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
age at first birth
educational attainment
gene-environment interaction
hidden heritability
human reproduction
missing heritability
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's