Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
26323059
TITLE
Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index.
ABSTRACT
We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing data. We demonstrate using simulations based on whole-genome sequencing data that ∼97% and ∼68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all ∼17 million imputed variants explain 56% (standard error (s.e.) = 2.3%) of variance for height and 27% (s.e. = 2.5%) of variance for body mass index (BMI), and we find evidence that height- and BMI-associated variants have been under natural selection. Considering the imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60-70% for height and 30-40% for BMI. Therefore, the missing heritability is small for both traits. For further discovery of genes associated with complex traits, a study design with SNP arrays followed by imputation is more cost-effective than whole-genome sequencing at current prices.
DATE PUBLISHED
2015 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/02/10
accepted 2015/07/31
entrez 2015/09/01 06:00
pubmed 2015/09/01 06:00
medline 2015/12/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Yang J Yang Jian J University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, Queensland, Australia.
Bakshi A Bakshi Andrew A Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Zhu Z Zhu Zhihong Z Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Hemani G Hemani Gibran G Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK.
Vinkhuyzen AA Vinkhuyzen Anna A E AA Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Lee SH Lee Sang Hong SH School of Environmental and Rural Science, University of New England, Armidale, New South Wales, Australia.
Robinson MR Robinson Matthew R MR Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Perry JR Perry John R B JR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Nolte IM Nolte Ilja M IM Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
van Vliet-Ostaptchouk JV van Vliet-Ostaptchouk Jana V JV Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
LifeLines Cohort Study
Esko T Esko Tonu T Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, Tartu, Estonia.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, Estonia.
Metspalu A Metspalu Andres A Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Hamsten A Hamsten Anders A Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Magnusson PK Magnusson Patrik K E PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ingelsson E Ingelsson Erik E Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Soranzo N Soranzo Nicole N Department of Haematology, University of Cambridge, Cambridge, UK.
Keller MC Keller Matthew C MC Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA.
Wray NR Wray Naomi R NR Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Goddard ME Goddard Michael E ME Biosciences Research Division, Department of Economic Development, Jobs, Transport and Resources, Bundoora, Victoria, Australia.
Visscher PM Visscher Peter M PM University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, Queensland, Australia.
INVESTIGATORS
JOURNAL
VOLUME: 47
ISSUE: 10
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2015
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
R01MH100141 NIMH NIH HHS United States
P01 GM099568 NIGMS NIH HHS United States
102215 Wellcome Trust United Kingdom
MC_UU_12015/2 Medical Research Council United Kingdom
MC_PC_15018 Medical Research Council United Kingdom
MC_U106179472 Medical Research Council United Kingdom
R01 MH100141 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Body Height genetics
Body Mass Index genetics
Genetic Variation genetics
Genome, Human genetics
Humans genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's