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; 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; Alex S F Doney; Andrew D Morris; Colin N A Palmer; 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 Winkler

Andrew 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, Alex S F Doney, Andrew D Morris, Colin N A Palmer, LifeLines Cohort Study

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

3540 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 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

Adipogenesis
Adiposity
Age Factors
Body Mass Index
Continental Population Groups
Energy Metabolism
Europe
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Glutamic Acid
Humans
Insulin
Male
Obesity
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Synapses

UN SDGs

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

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10.1038/nature14177

Doney, Alexander
- Cardiovascular Research - Clinical Reader (Teaching and Research)
Person: Academic

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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{f54aa4ca8ca54c34a4b27bba8610a1b4,

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 = "Adipogenesis, Adiposity, Age Factors, Body Mass Index, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Male, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses",

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 Hedman, \{{\AA}sa K\} and Juha Karjalainen and Schmidt, \{Ellen M\} and Devin Absher and Najaf Amin and Denise Anderson and Marian Beekman and Bolton, \{Jennifer L\} and Bragg-Gresham, \{Jennifer L\} and Steven Buyske and Ayse Demirkan and Guohong Deng and Ehret, \{Georg B\} and Bjarke Feenstra and Feitosa, \{Mary F\} and Krista Fischer and Anuj Goel and Jian Gong and Jackson, \{Anne U\} and Doney, \{Alex S F\} and Morris, \{Andrew D\} and Palmer, \{Colin N A\} 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 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, 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, Doney, ASF, Morris, AD, Palmer, CNA & 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 - 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 - Doney, Alex S F

AU - Morris, Andrew D

AU - Palmer, Colin N A

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 - Adipogenesis

KW - Adiposity

KW - Age Factors

KW - Body Mass Index

KW - Continental Population Groups

KW - Energy Metabolism

KW - Europe

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Glutamic Acid

KW - Humans

KW - Insulin

KW - Male

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Synapses

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

UN SDGs

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Doney, Alexander

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