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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 |
|
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 |
|
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|
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| 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 |
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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. |
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| INVESTIGATORS |
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| 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 |
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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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