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

The LifeLines Cohort Study; The ADIPOGen Consortium; The AGEN-BMI Working Group; The CARDIOGRAMplusC4D Consortium; The CKDGen Consortium; GLGC Consortium; The ICBP; The MAGIC Investigators; The MuTHER Consortium; The MIGen Consortium; The PAGE Consortium; The ReproGen Consortium; The GENIE Consortium; The International 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; 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; Christina Willenborg; Jeanette Erdmann; Heribert Schunkert

doi:10.1038/nature14177

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

The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, GLGC Consortium, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International 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, 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, Christina Willenborg, Jeanette Erdmann, Heribert Schunkert

801 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
Journal	Nature
Volume	518
Issue number	7538
Pages (from-to)	197-206
Number of pages	10
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature14177
Publication status	Published - 12.02.2015

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10.1038/nature14177

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The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, GLGC Consortium, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., ... Schunkert, H. (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{cf5ac1de2d5e438f881bb630a423f536,

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.",

author = "{The LifeLines Cohort Study} and {The ADIPOGen Consortium} and {The AGEN-BMI Working Group} and {The CARDIOGRAMplusC4D Consortium} and {The CKDGen Consortium} and {GLGC Consortium} and {The ICBP} and {The MAGIC Investigators} and {The MuTHER Consortium} and {The MIGen Consortium} and {The PAGE Consortium} and {The ReproGen Consortium} and {The GENIE Consortium} and {The International 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 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 Zhao, {Jing Hua} 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 Christina Willenborg and Jeanette Erdmann and Heribert Schunkert",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14177",

language = "English",

volume = "518",

pages = "197--206",

journal = "Nature",

issn = "0028-0836",

number = "7538",

}

The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, GLGC Consortium, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International 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, Mägi, R, Randall, JC, Winkler, TW, Wood, AR, Workalemahu, T, Faul, JD, Smith, JA, Zhao, JH, 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, Willenborg, C, Erdmann, J & Schunkert, H 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 - The LifeLines Cohort Study

AU - The ADIPOGen Consortium

AU - The AGEN-BMI Working Group

AU - The CARDIOGRAMplusC4D Consortium

AU - The CKDGen Consortium

AU - GLGC Consortium

AU - The ICBP

AU - The MAGIC Investigators

AU - The MuTHER Consortium

AU - The MIGen Consortium

AU - The PAGE Consortium

AU - The ReproGen Consortium

AU - The GENIE Consortium

AU - The International 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, 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 - Zhao, Jing Hua

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 - Willenborg, Christina

AU - Erdmann, Jeanette

AU - Schunkert, Heribert

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.

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U2 - 10.1038/nature14177

DO - 10.1038/nature14177

M3 - Journal articles

C2 - 25673413

AN - SCOPUS:84923171580

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

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