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PMID |
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TITLE |
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Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Yang J |
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Yang |
Jian |
J |
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University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, Queensland, Australia. |
Bakshi A |
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Bakshi |
Andrew |
A |
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Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. |
Zhu Z |
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Zhu |
Zhihong |
Z |
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Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. |
Hemani G |
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Hemani |
Gibran |
G |
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Medical Research Council (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, Bristol, UK. |
Vinkhuyzen AA |
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Vinkhuyzen |
Anna A E |
AA |
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Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. |
Lee SH |
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Lee |
Sang Hong |
SH |
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School of Environmental and Rural Science, University of New England, Armidale, New South Wales, Australia. |
Robinson MR |
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Robinson |
Matthew R |
MR |
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Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. |
Perry JR |
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Perry |
John R B |
JR |
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MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK. |
Nolte IM |
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Nolte |
Ilja M |
IM |
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Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. |
van Vliet-Ostaptchouk JV |
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van Vliet-Ostaptchouk |
Jana V |
JV |
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Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. |
Snieder H |
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Snieder |
Harold |
H |
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Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. |
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LifeLines Cohort Study |
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Esko T |
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Esko |
Tonu |
T |
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Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. |
Milani L |
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Milani |
Lili |
L |
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Estonian Genome Center, University of Tartu, Tartu, Estonia. |
Mägi R |
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Mägi |
Reedik |
R |
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Estonian Genome Center, University of Tartu, Tartu, Estonia. |
Metspalu A |
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Metspalu |
Andres |
A |
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Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. |
Hamsten A |
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Hamsten |
Anders |
A |
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Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. |
Magnusson PK |
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Magnusson |
Patrik K E |
PK |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
Pedersen NL |
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Pedersen |
Nancy L |
NL |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
Ingelsson E |
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Ingelsson |
Erik |
E |
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Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. |
Soranzo N |
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Soranzo |
Nicole |
N |
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Department of Haematology, University of Cambridge, Cambridge, UK. |
Keller MC |
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Keller |
Matthew C |
MC |
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Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA. |
Wray NR |
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Wray |
Naomi R |
NR |
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Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. |
Goddard ME |
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Goddard |
Michael E |
ME |
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Biosciences Research Division, Department of Economic Development, Jobs, Transport and Resources, Bundoora, Victoria, Australia. |
Visscher PM |
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Visscher |
Peter M |
PM |
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University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, Queensland, Australia. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 47 |
ISSUE: 10 |
TITLE: Nature genetics |
ISOABBREVIATION: Nat. Genet. |
YEAR: 2015 |
MONTH: Oct |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1546-1718 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Nat Genet |
COUNTRY: United States |
ISSNLINKING: 1061-4036 |
NLMUNIQUEID: 9216904 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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GRANTS |
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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 |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Body Height |
genetics |
Body Mass Index |
genetics |
Genetic Variation |
genetics |
Genome, Human |
genetics |
Humans |
genetics |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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