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 Winkler; Andrew R Wood; Tsegaselassie Workalemahu; Jessica D Faul; Jennifer A Smith; Jing Hua Zhao; Wei Zhao; Jin Chen; Rudolf Fehrmann; Juha Karjalainen; Irene Mateo Leach; Jana V Van Vliet-Ostaptchouk; Marcel Bruinenberg; Catharina A Hartman; Ilja M Nolte; Salome Scholtens; Joanna Smolonska; Morris A Swertz; Niek Verweij; Judith M Vonk; Harm-Jan Westra; Stephan J L Bakker; Ron T Gansevoort; Meena Kumari; Albertine J Oldehinkel; Dirkje S Postma; Ronald P Stolk; Folkert W Asselbergs; Harold Snieder; Pim van der Harst; Lude Franke; Lifelines Cohort Study

doi:10.1038/nature14177

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, Juha Karjalainen, Irene Mateo Leach, Jana V Van Vliet-Ostaptchouk, Marcel Bruinenberg, Catharina A Hartman, Ilja M Nolte, Salome Scholtens, Joanna Smolonska, Morris A Swertz, Niek Verweij, Judith M Vonk, Harm-Jan Westra, Stephan J L Bakker, Ron T Gansevoort, Meena Kumari, Albertine J Oldehinkel, Dirkje S Postma, Ronald P Stolk, Folkert W Asselbergs, Harold Snieder, Pim van der Harst, Lude Franke, Lifelines Cohort Study

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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
Publication status	Published - 12-Feb-2015

Keywords

GENOME-WIDE ASSOCIATION
PROVIDES INSIGHTS
GLYCEMIC TRAITS
HUMAN HEIGHT
LOCI
METAANALYSIS
VARIANTS
EXPRESSION
PATHWAYS
ARCHITECTURE

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Genetic studies of body mass index yield new insights for obesity biology
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Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., Day, F. R., Powell, C., Vedantam, S., Buchkovich, M. L., Yang, J., Croteau-Chonka, D. C., Esko, T., Fall, T., Ferreira, T., Gustafsson, S., Kutalik, Z., Luan, J., Mägi, R., Randall, J. C., ... 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

@article{f59d7c8e02b04077b24ca604d61afca9,

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.",

keywords = "GENOME-WIDE ASSOCIATION, PROVIDES INSIGHTS, GLYCEMIC TRAITS, HUMAN HEIGHT, LOCI, METAANALYSIS, VARIANTS, EXPRESSION, PATHWAYS, ARCHITECTURE",

author = "Locke, {Adam E} and Bratati Kahali and Berndt, {Sonja I} and Justice, {Anne E} and Pers, {Tune H} and Day, {Felix R} and Corey Powell and Sailaja Vedantam and Buchkovich, {Martin L} and Jian Yang and Croteau-Chonka, {Damien C} and Tonu Esko and Tove Fall and Teresa Ferreira and Stefan Gustafsson and Zolt{\'a}n Kutalik and Jian'an Luan and Reedik M{\"a}gi and Randall, {Joshua C} and Winkler, {Thomas W} and Wood, {Andrew R} and Tsegaselassie Workalemahu and Faul, {Jessica D} and Smith, {Jennifer A} and {Hua Zhao}, Jing and Wei Zhao and Jin Chen and Rudolf Fehrmann and Juha Karjalainen and {Mateo Leach}, Irene and {Van Vliet-Ostaptchouk}, {Jana V} and Marcel Bruinenberg and Hartman, {Catharina A} and Nolte, {Ilja M} and Salome Scholtens and Joanna Smolonska and Swertz, {Morris A} and Niek Verweij and Vonk, {Judith M} and Harm-Jan Westra and Bakker, {Stephan J L} and Gansevoort, {Ron T} and Meena Kumari and Oldehinkel, {Albertine J} and Postma, {Dirkje S} and Stolk, {Ronald P} and Asselbergs, {Folkert W} and Harold Snieder and {van der Harst}, Pim and Lude Franke and {Lifelines Cohort Study}",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14177",

language = "English",

volume = "518",

pages = "197--206",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7538",

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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, Karjalainen, J, Mateo Leach, I , Van Vliet-Ostaptchouk, JV , Bruinenberg, M , Hartman, CA , Nolte, IM , Scholtens, S, Smolonska, J, Swertz, MA, Verweij, N, Vonk, JM , Westra, H-J , Bakker, SJL , Gansevoort, RT, Kumari, M, Oldehinkel, AJ, Postma, DS, Stolk, RP, Asselbergs, FW, Snieder, H , van der Harst, P , Franke, L & 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

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 - Karjalainen, Juha

AU - Mateo Leach, Irene

AU - Van Vliet-Ostaptchouk, Jana V

AU - Bruinenberg, Marcel

AU - Hartman, Catharina A

AU - Nolte, Ilja M

AU - Scholtens, Salome

AU - Smolonska, Joanna

AU - Swertz, Morris A

AU - Verweij, Niek

AU - Vonk, Judith M

AU - Westra, Harm-Jan

AU - Bakker, Stephan J L

AU - Gansevoort, Ron T

AU - Kumari, Meena

AU - Oldehinkel, Albertine J

AU - Postma, Dirkje S

AU - Stolk, Ronald P

AU - Asselbergs, Folkert W

AU - Snieder, Harold

AU - van der Harst, Pim

AU - Franke, Lude

AU - Lifelines Cohort Study

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.

KW - GENOME-WIDE ASSOCIATION

KW - PROVIDES INSIGHTS

KW - GLYCEMIC TRAITS

KW - HUMAN HEIGHT

KW - LOCI

KW - METAANALYSIS

KW - VARIANTS

KW - EXPRESSION

KW - PATHWAYS

KW - ARCHITECTURE

U2 - 10.1038/nature14177

DO - 10.1038/nature14177

M3 - Article

C2 - 25673413

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

Keywords

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