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

Adam E Locke, Bratati Kahali, Sonja I Berndt, Anne E Justice, Tune H Pers, Felix R Day, Corey Powell, Sailaja Vedantam, Martin L Buchkovich, Jian Yang, Damien C Croteau-Chonka, Tonu Esko, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Zoltán Kutalik, Jian'an Luan, Reedik Mägi, Joshua C Randall, Thomas W WinklerAndrew R Wood, Tsegaselassie Workalemahu, Jessica D Faul, Jennifer A Smith, Jing Hua Zhao, Wei Zhao, Jin Chen, Rudolf Fehrmann, Åsa K Hedman, Juha Karjalainen, Ellen M Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L Bolton, Jennifer L Bragg-Gresham, Steven Buyske, Ayse Demirkan, Guohong Deng, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Anuj Goel, Jian Gong, Anne U Jackson, Stavroula Kanoni, Eoin P Brennan, Amy J McKnight, LifeLines Cohort Study

Research output: Contribution to journalArticle

1477 Citations (Scopus)

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 languageEnglish
Pages (from-to)197-206
Number of pages10
JournalNature
Volume518
Issue number7538
Early online date11 Feb 2015
DOIs
Publication statusPublished - 12 Feb 2015

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Body Mass Index
Obesity
Adipogenesis
Genome-Wide Association Study
Adiposity
Energy Metabolism
Meta-Analysis
Glutamic Acid
Central Nervous System
Insulin
Lipids
Genes

Cite this

Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., Day, F. R., ... LifeLines Cohort Study (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-206. https://doi.org/10.1038/nature14177
Locke, Adam E ; Kahali, Bratati ; Berndt, Sonja I ; Justice, Anne E ; Pers, Tune H ; Day, Felix R ; Powell, Corey ; Vedantam, Sailaja ; Buchkovich, Martin L ; Yang, Jian ; Croteau-Chonka, Damien C ; Esko, Tonu ; Fall, Tove ; Ferreira, Teresa ; Gustafsson, Stefan ; Kutalik, Zoltán ; Luan, Jian'an ; Mägi, Reedik ; Randall, Joshua C ; Winkler, Thomas W ; Wood, Andrew R ; Workalemahu, Tsegaselassie ; Faul, Jessica D ; Smith, Jennifer A ; Hua Zhao, Jing ; Zhao, Wei ; Chen, Jin ; Fehrmann, Rudolf ; Hedman, Åsa K ; Karjalainen, Juha ; Schmidt, Ellen M ; Absher, Devin ; Amin, Najaf ; Anderson, Denise ; Beekman, Marian ; Bolton, Jennifer L ; Bragg-Gresham, Jennifer L ; Buyske, Steven ; Demirkan, Ayse ; Deng, Guohong ; Ehret, Georg B ; Feenstra, Bjarke ; Feitosa, Mary F ; Fischer, Krista ; Goel, Anuj ; Gong, Jian ; Jackson, Anne U ; Kanoni, Stavroula ; Brennan, Eoin P ; McKnight, Amy J ; LifeLines Cohort Study. / Genetic studies of body mass index yield new insights for obesity biology. In: Nature. 2015 ; Vol. 518, No. 7538. pp. 197-206.
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Locke, AE, Kahali, B, Berndt, SI, Justice, AE, Pers, TH, Day, FR, Powell, C, Vedantam, S, Buchkovich, ML, Yang, J, Croteau-Chonka, DC, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J, Mägi, R, Randall, JC, Winkler, TW, Wood, AR, Workalemahu, T, Faul, JD, Smith, JA, Hua Zhao, J, Zhao, W, Chen, J, Fehrmann, R, Hedman, ÅK, Karjalainen, J, Schmidt, EM, Absher, D, Amin, N, Anderson, D, Beekman, M, Bolton, JL, Bragg-Gresham, JL, Buyske, S, Demirkan, A, Deng, G, Ehret, GB, Feenstra, B, Feitosa, MF, Fischer, K, Goel, A, Gong, J, Jackson, AU, Kanoni, S, Brennan, EP, McKnight, AJ & LifeLines Cohort Study 2015, 'Genetic studies of body mass index yield new insights for obesity biology', Nature, vol. 518, no. 7538, pp. 197-206. https://doi.org/10.1038/nature14177

Genetic studies of body mass index yield new insights for obesity biology. / Locke, Adam E; Kahali, Bratati; Berndt, Sonja I; Justice, Anne E; Pers, Tune H; Day, Felix R; Powell, Corey; Vedantam, Sailaja; Buchkovich, Martin L; Yang, Jian; Croteau-Chonka, Damien C; Esko, Tonu; Fall, Tove; Ferreira, Teresa; Gustafsson, Stefan; Kutalik, Zoltán; Luan, Jian'an; Mägi, Reedik; Randall, Joshua C; Winkler, Thomas W; Wood, Andrew R; Workalemahu, Tsegaselassie; Faul, Jessica D; Smith, Jennifer A; Hua Zhao, Jing; Zhao, Wei; Chen, Jin; Fehrmann, Rudolf; Hedman, Åsa K; Karjalainen, Juha; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bolton, Jennifer L; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Deng, Guohong; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Goel, Anuj; Gong, Jian; Jackson, Anne U; Kanoni, Stavroula; Brennan, Eoin P; McKnight, Amy J; LifeLines Cohort Study.

In: Nature, Vol. 518, No. 7538, 12.02.2015, p. 197-206.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Locke, Adam E

AU - Kahali, Bratati

AU - Berndt, Sonja I

AU - Justice, Anne E

AU - Pers, Tune H

AU - Day, Felix R

AU - Powell, Corey

AU - Vedantam, Sailaja

AU - Buchkovich, Martin L

AU - Yang, Jian

AU - Croteau-Chonka, Damien C

AU - Esko, Tonu

AU - Fall, Tove

AU - Ferreira, Teresa

AU - Gustafsson, Stefan

AU - Kutalik, Zoltán

AU - Luan, Jian'an

AU - Mägi, Reedik

AU - Randall, Joshua C

AU - Winkler, Thomas W

AU - Wood, Andrew R

AU - Workalemahu, Tsegaselassie

AU - Faul, Jessica D

AU - Smith, Jennifer A

AU - Hua Zhao, Jing

AU - Zhao, Wei

AU - Chen, Jin

AU - Fehrmann, Rudolf

AU - Hedman, Åsa K

AU - Karjalainen, Juha

AU - Schmidt, Ellen M

AU - Absher, Devin

AU - Amin, Najaf

AU - Anderson, Denise

AU - Beekman, Marian

AU - Bolton, Jennifer L

AU - Bragg-Gresham, Jennifer L

AU - Buyske, Steven

AU - Demirkan, Ayse

AU - Deng, Guohong

AU - Ehret, Georg B

AU - Feenstra, Bjarke

AU - Feitosa, Mary F

AU - Fischer, Krista

AU - Goel, Anuj

AU - Gong, Jian

AU - Jackson, Anne U

AU - Kanoni, Stavroula

AU - Brennan, Eoin P

AU - McKnight, Amy J

AU - LifeLines Cohort Study

PY - 2015/2/12

Y1 - 2015/2/12

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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.

U2 - 10.1038/nature14177

DO - 10.1038/nature14177

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Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015 Feb 12;518(7538):197-206. https://doi.org/10.1038/nature14177