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; Peter E H Schwarz; Mads Melbye; Inger Njølstad; 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, 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, Peter E H Schwarz, Mads Melbye, Inger Njølstad, LifeLines Cohort Study

Institut for Klinisk Medicin

1998 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	14177
Tidsskrift	Nature
Vol/bind	518
Udgave nummer	7538
Sider (fra-til)	197-206
Antal sider	24
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature14177
Status	Udgivet - 12 feb. 2015

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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. [14177]. https://doi.org/10.1038/nature14177

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, Schwarz, PEH , Melbye, M, Njølstad, I & LifeLines Cohort Study 2015, 'Genetic studies of body mass index yield new insights for obesity biology', Nature, bind 518, nr. 7538, 14177, s. 197-206. https://doi.org/10.1038/nature14177

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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 Schwarz, {Peter E H} and Mads Melbye and Inger Nj{\o}lstad and {LifeLines Cohort Study}",

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month = feb,

day = "12",

doi = "10.1038/nature14177",

language = "English",

volume = "518",

pages = "197--206",

journal = "Nature",

issn = "0028-0836",

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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 - Schwarz, Peter E H

AU - Melbye, Mads

AU - Njølstad, Inger

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 - Journal article

C2 - 25673413

SN - 0028-0836

VL - 518

SP - 197

EP - 206

JO - Nature

JF - Nature

IS - 7538

M1 - 14177

ER -

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

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