Genetic studies of body mass index yield new insights for obesity biology

doi:10.1038/nature14177

Genetic studies of body mass index yield new insights for obesity biology

,

Research output: Contribution to journal › Article › peer-review

3514 Scopus citations

Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10^-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Original language	English
Pages (from-to)	197-206
Number of pages	10
Journal	Nature
Volume	518
Issue number	7538
DOIs	https://doi.org/10.1038/nature14177
State	Published - Feb 12 2015

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

Funding

Funders	Funder number
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	P30CA071789, UM1CA182910, UM1CA182913, U01CA164930
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK072193, P30DK072488, R01DK089256, U01DK062370, P30DK020572, P30DK063491, R01DK075787, P30DK020541, R01DK078150, K23DK080145, R01DK093757
UK Medical Research Council, Engineering and Physical Sciences Research Council	MR/N01104X/1, G0601261, MC_UP_A100_1003, MR/K002414/1, MC_UU_12019/1, MC_UU_12015/5, MC_U106179471, MC_UU_12015/2, G0600717, MR/K013351/1, MC_UU_12015/1, MR/L003120/1, MC_UU_12013/1, G9521010, MC_UU_12012/1, G19/35, G0401527, MR/K006584/1, G1001799, MC_PC_U127561128, G0902037, G0100222, G1000616
National Institute on Minority Health and Health Disparities (NIMHD)	P20MD006899
National Institute on Aging	R01AG033193, R01AG041517, R01AG025941, U01AG049505, U01AG009740, ZIAAG000675
National Human Genome Research Institute	U01HG007376, U01HG007416, U01HG007419, U01HG007417
Horizon 2020 Framework Programme	692065, 692145
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	T32GM080178, P30GM103341, R25GM062459, T32GM007814
National Heart, Lung, and Blood Institute (NHLBI)	R01HL105756, R01HL109946, T32HL007824, R01HL117078, K01HL116770, R01HL117626, T32HL007055, P30HL107251
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS017950
National Center for Advancing Translational Sciences (NCATS)	UL1TR000124, TL1TR001066, UL1TR001067
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	152578, 143914
Australian National Health and Medical Research Council	454382
European Commission	323195, 322698
Economic and Social Research Council	ES/J023299/1, ES/F02679X/1
Not added	864.13.013
National Institute on Drug Abuse	R21DA027040

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature14177

Cite this

@article{78149bc946a548ff8b2612298eea6a3d,

title = "Genetic studies of body mass index yield new insights for obesity biology",

abstract = "Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7\% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 \% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.",

author = "Locke, \{A. E.\} and B. Kahali and Berndt, \{S. I.\} and Justice, \{A. E.\} and Pers, \{T. H.\} and Day, \{F. R.\} and C. Powell and S. Vedantam and Buchkovich, \{M. L.\} and J. Yang and Croteau-Chonka, \{D. C.\} and T. Esko and T. Fall and T. Ferreira and S. Gustafsson and Z. Kutalik and J. Luan and R. M{\"a}gi and Randall, \{J. C.\} and Winkler, \{T. W.\} and Wood, \{A. R.\} and T. Workalemahu and Faul, \{J. D.\} and Smith, \{J. A.\} and Zhao, \{J. H.\} and W. Zhao and J. Chen and R. Fehrmann and K. Hedman and J. Karjalainen and Schmidt, \{E. M.\} and D. Absher and N. Amin and D. Anderson and M. Beekman and Bolton, \{J. L.\} and Bragg-Gresham, \{J. L.\} and S. Buyske and A. Demirkan and G. Deng and Ehret, \{G. B.\} and B. Feenstra and Feitosa, \{M. F.\} and K. Fischer and A. Goel and J. Gong and Jackson, \{A. U.\} and S. Kanoni and Kleber, \{M. E.\} and C. He",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14177",

language = "English",

volume = "518",

pages = "197--206",

number = "7538",

}

TY - JOUR

T1 - Genetic studies of body mass index yield new insights for obesity biology

AU - Locke, A. E.

AU - Kahali, B.

AU - Berndt, S. I.

AU - Justice, A. E.

AU - Pers, T. H.

AU - Day, F. R.

AU - Powell, C.

AU - Vedantam, S.

AU - Buchkovich, M. L.

AU - Yang, J.

AU - Croteau-Chonka, D. C.

AU - Esko, T.

AU - Fall, T.

AU - Ferreira, T.

AU - Gustafsson, S.

AU - Kutalik, Z.

AU - Luan, J.

AU - Mägi, R.

AU - Randall, J. C.

AU - Winkler, T. W.

AU - Wood, A. R.

AU - Workalemahu, T.

AU - Faul, J. D.

AU - Smith, J. A.

AU - Zhao, J. H.

AU - Zhao, W.

AU - Chen, J.

AU - Fehrmann, R.

AU - Hedman, K.

AU - Karjalainen, J.

AU - Schmidt, E. M.

AU - Absher, D.

AU - Amin, N.

AU - Anderson, D.

AU - Beekman, M.

AU - Bolton, J. L.

AU - Bragg-Gresham, J. L.

AU - Buyske, S.

AU - Demirkan, A.

AU - Deng, G.

AU - Ehret, G. B.

AU - Feenstra, B.

AU - Feitosa, M. F.

AU - Fischer, K.

AU - Goel, A.

AU - Gong, J.

AU - Jackson, A. U.

AU - Kanoni, S.

AU - Kleber, M. E.

AU - He, C.

PY - 2015/2/12

Y1 - 2015/2/12

N2 - Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

AB - Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84923171580&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923171580&partnerID=8YFLogxK

U2 - 10.1038/nature14177

DO - 10.1038/nature14177

M3 - Article

C2 - 25673413

AN - SCOPUS:84923171580

SN - 0028-0836

VL - 518

SP - 197

EP - 206

JO - Nature

JF - Nature

IS - 7538

ER -

Genetic studies of body mass index yield new insights for obesity biology

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this