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

,

Producción científica: Article › revisión exhaustiva

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Resumen

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.

Idioma original	English
Páginas (desde-hasta)	197-206
Número de páginas	10
Publicación	Nature
Volumen	518
N.º	7538
DOI	https://doi.org/10.1038/nature14177
Estado	Published - feb 12 2015

Nota bibliográfica

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

Financiación

Financiadores	Número del financiador
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, U01DK062370, P30DK020572, R01DK089256, P30DK063491, P60DK020541, R01DK075787, 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
???publication-publication-funding-organisation-not-added???	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
???publication-publication-funding-organisation-not-added???	R01NS017950
???publication-publication-funding-organisation-not-added???	R01HL105756, R01HL109946, T32HL007824, R01HL117078, K01HL116770, R01HL117626, T32HL007055, P30HL107251
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
???publication-publication-funding-organisation-not-added???	864.13.013
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse	R21DA027040

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General

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10.1038/nature14177

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@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",

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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.

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U2 - 10.1038/nature14177

DO - 10.1038/nature14177

M3 - Article

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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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

Acceder al documento

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Huella

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