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; Zoltan Kutalik; Jian'an Luan; Reedik Maegi; 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; Asa K. Hedman; Juha Karjalainen; Ellen M. Schmidt; Devin Absher; Najaf Amin; Denise Anderson; Sander W. van der Laan; Jessica van Setten; Hae-Won Uh; Hester M. den Ruijter; Frans L. Moll; Gerard Pasterkamp; Folkert W. Asselbergs; Paul I. W. de Bakker; Pieter Zanen

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
, Zoltan Kutalik
, Jian'an Luan
, Reedik Maegi
, 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, Asa K. Hedman, Juha Karjalainen, Ellen M. Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Sander W. van der Laan, Jessica van Setten, Hae-Won Uh, Hester M. den Ruijter, Frans L. Moll, Gerard Pasterkamp, Folkert W. Asselbergs, Paul I. W. de Bakker, Pieter Zanen, , , , , , , , , , , , , ,

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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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P <5 x 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 similar to 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 systemin 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
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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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., Maegi, R., Randall, J. C. (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{4935e6bca7a543ba9c2aab2db25c69ea,

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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P <5 x 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 similar to 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 systemin 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 Zoltan Kutalik and Jian'an Luan and Reedik Maegi and Randall, \{Joshua C.\} and Winkler, \{Thomas W.\} and Wood, \{Andrew R.\} and Tsegaselassie Workalemahu and Faul, \{Jessica D.\} and Smith, \{Jennifer A.\} and Zhao, \{Jing Hua\} and Wei Zhao and Jin Chen and Rudolf Fehrmann and Hedman, \{Asa K.\} and Juha Karjalainen and Schmidt, \{Ellen M.\} and Devin Absher and Najaf Amin and Denise Anderson and \{van der Laan\}, \{Sander W.\} and \{van Setten\}, Jessica and Hae-Won Uh and \{den Ruijter\}, \{Hester M.\} and Moll, \{Frans L.\} and Gerard Pasterkamp and Asselbergs, \{Folkert W.\} and \{de Bakker\}, \{Paul I. W.\} and Pieter Zanen and P Peeters and FJM Broekmans and \{van Gils\}, CH and \{van der Schouw\}, YT and BCJM Fauser and C.S.P.M. Uiterwaal and Bots, \{Michael L\}",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14177",

language = "English",

volume = "518",

pages = "197--206",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7538",

}

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, Maegi, R, Randall, JC, Winkler, TW, Wood, AR, Workalemahu, T, Faul, JD, Smith, JA, Zhao, JH, Zhao, W, Chen, J, Fehrmann, R, Hedman, AK, Karjalainen, J, Schmidt, EM, Absher, D, Amin, N, Anderson, D, van der Laan, SW , van Setten, J , Uh, H-W , den Ruijter, HM, Moll, FL, Pasterkamp, G , Asselbergs, FW, de Bakker, PIW, Zanen, P 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, Zoltan

AU - Luan, Jian'an

AU - Maegi, 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 - Zhao, Jing Hua

AU - Zhao, Wei

AU - Chen, Jin

AU - Fehrmann, Rudolf

AU - Hedman, Asa K.

AU - Karjalainen, Juha

AU - Schmidt, Ellen M.

AU - Absher, Devin

AU - Amin, Najaf

AU - Anderson, Denise

AU - van der Laan, Sander W.

AU - van Setten, Jessica

AU - Uh, Hae-Won

AU - den Ruijter, Hester M.

AU - Moll, Frans L.

AU - Pasterkamp, Gerard

AU - Asselbergs, Folkert W.

AU - de Bakker, Paul I. W.

AU - Zanen, Pieter

AU - Peeters, P

AU - Broekmans, FJM

AU - van Gils, CH

AU - van der Schouw, YT

AU - Fauser, BCJM

AU - Uiterwaal, C.S.P.M.

AU - Bots, Michael L

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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P <5 x 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 similar to 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 systemin 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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P <5 x 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 similar to 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 systemin 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

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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