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

LifeLines Cohort Study; ADIPOGen Consortium; AGEN-BMI Working Grp; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; Int Endogene Consortium; 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; Marian Beekman; Jennifer L. Bolton; L. Bragg-Gresham; Steven Buyske; Ayse Demirkan; Guohong Deng; Ross M. Fraser; Caroline Hayward; Stela McLachlan; Harry Campbell; Andrew D. Morris; Jackie F. Price; Igor Rudan; Mark Walker; James F. Wilson; Peter M. Visscher

doi:10.1038/nature14177

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

LifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Grp, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, Int Endogene Consortium, Adam E. Locke, Bratati Kahali, Sonja I. Berndt, Anne E. Justice, Tune H. Pers, Felix R. DayCorey 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, Marian Beekman, Jennifer L. Bolton, L. Bragg-Gresham, Steven Buyske, Ayse Demirkan, Guohong Deng, Ross M. Fraser, Caroline Hayward, Stela McLachlan, Harry Campbell, Andrew D. Morris, Jackie F. Price, Igor Rudan, Mark Walker, James F. Wilson, Peter M. Visscher

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

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-U401
Number of pages	23
Journal	Nature
Volume	518
Issue number	7538
Early online date	11 Feb 2015
DOIs	https://doi.org/10.1038/nature14177
Publication status	Published - 12 Feb 2015

Keywords / Materials (for Non-textual outputs)

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

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10.1038/nature14177

Genetic studies of body mass index yield new insights for obesity biology
This is the author's accepted and peer-reviewed manuscript, available in PMC 2015 April 1.
Accepted author manuscript, 1.28 MB

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LifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Grp, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, Int Endogene Consortium, Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., ... Visscher, P. M. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-U401. 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 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 = "{LifeLines Cohort Study} and {ADIPOGen Consortium} and {AGEN-BMI Working Grp} and {CARDIOGRAMplusC4D Consortium} and {CKDGen Consortium} and GLGC and ICBP and {MAGIC Investigators} and {MuTHER Consortium} and {MIGen Consortium} and {PAGE Consortium} and {ReproGen Consortium} and {GENIE Consortium} and {Int Endogene Consortium} and 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 Marian Beekman and Bolton, {Jennifer L.} and L. Bragg-Gresham and Steven Buyske and Ayse Demirkan and Guohong Deng and Fraser, {Ross M.} and Caroline Hayward and Stela McLachlan and Harry Campbell and Morris, {Andrew D.} and Price, {Jackie F.} and Igor Rudan and Mark Walker and Wilson, {James F.} and Visscher, {Peter M.}",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14177",

language = "English",

volume = "518",

pages = "197--U401",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7538",

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LifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Grp, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, Int Endogene Consortium, 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, Beekman, M, Bolton, JL, Bragg-Gresham, L, Buyske, S, Demirkan, A, Deng, G, Fraser, RM, Hayward, C, McLachlan, S, Campbell, H , Morris, AD , Price, JF , Rudan, I, Walker, M, Wilson, JF & Visscher, PM 2015, 'Genetic studies of body mass index yield new insights for obesity biology', Nature, vol. 518, no. 7538, pp. 197-U401. https://doi.org/10.1038/nature14177

TY - JOUR

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

AU - LifeLines Cohort Study

AU - ADIPOGen Consortium

AU - AGEN-BMI Working Grp

AU - CARDIOGRAMplusC4D Consortium

AU - CKDGen Consortium

AU - GLGC

AU - ICBP

AU - MAGIC Investigators

AU - MuTHER Consortium

AU - MIGen Consortium

AU - PAGE Consortium

AU - ReproGen Consortium

AU - GENIE Consortium

AU - Int Endogene Consortium

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 - Beekman, Marian

AU - Bolton, Jennifer L.

AU - Bragg-Gresham, L.

AU - Buyske, Steven

AU - Demirkan, Ayse

AU - Deng, Guohong

AU - Fraser, Ross M.

AU - Hayward, Caroline

AU - McLachlan, Stela

AU - Campbell, Harry

AU - Morris, Andrew D.

AU - Price, Jackie F.

AU - Rudan, Igor

AU - Walker, Mark

AU - Wilson, James F.

AU - Visscher, Peter M.

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-U401

JO - Nature

JF - Nature

IS - 7538

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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