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

ADIPOGen Consortium; The AGEN-BMI Working Group; The CARDIOGRAMplusC4D Consortium; The CKDGen Consortium; The GLGC; ICBP Consortium; The MAGIC Investigators; The MuTHER Consortium; The MIGen Consortium; The PAGE Consortium; The GENIE Consortium; The International Endogene Consortium; Adam E Locke; Bratati Kahali; The LifeLines Cohort Study; ReproGen Consortium; 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; Ayse Demirkan; Marjolein J Peters; Alexander Teumer; Sander W van der Laan; Aaron Isaacs; Jouke-Jan Hottenga; Frank C Verhulst; Niek Verweij; John R B Perry; Lisette Stolk; Albert Hofman; M Carola Zillikens; Yongmei Liu; Ben A Oostra; Fernando Rivadeneira; André G Uitterlinden; Cornelia M van Duijn; Oscar Franco Duran; JCM Witteman; Maria Medina Gomez; Karol Estrada Gil; Ruth J.F. Loos; EK Speliotes

doi:10.1038/nature14177

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

ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, ICBP Consortium, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The GENIE Consortium, The International Endogene Consortium, Adam E Locke, Bratati Kahali, The LifeLines Cohort Study, ReproGen Consortium, 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, Ayse Demirkan, Marjolein J Peters, Alexander Teumer, Sander W van der Laan, Aaron Isaacs, Jouke-Jan Hottenga, Frank C Verhulst, Niek Verweij, John R B Perry, Lisette Stolk, Albert Hofman, M Carola Zillikens, Yongmei Liu, Ben A Oostra, Fernando Rivadeneira, André G Uitterlinden, Cornelia M van Duijn, Oscar Franco Duran, JCM Witteman, Maria Medina Gomez, Karol Estrada Gil, Ruth J.F. Loos, EK Speliotes

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

3387 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 - 11 Feb 2015

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EMC COEUR-09
EMC MGC-02-96-01
EMC MM-01-39-04
EMC MM-01-39-09-A
EMC MM-01-52-07
EMC NIHES-01-64-02
EMC NIHES-04-55-01
EMC OR-01-39-08

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

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10.1038/nature14177

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ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, ICBP Consortium, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The GENIE Consortium, The International Endogene Consortium, Locke, A. E., Kahali, B., The LifeLines Cohort Study, ReproGen Consortium, Berndt, S. I., Justice, A. E., Pers, T. H., ... Speliotes, EK. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 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.",

author = "{ADIPOGen Consortium} and {The AGEN-BMI Working Group} and {The CARDIOGRAMplusC4D Consortium} and {The CKDGen Consortium} and {The GLGC} and {ICBP Consortium} and {The MAGIC Investigators} and {The MuTHER Consortium} and {The MIGen Consortium} and {The PAGE Consortium} and {The GENIE Consortium} and {The International Endogene Consortium} and Locke, {Adam E} and Bratati Kahali and {The LifeLines Cohort Study} and {ReproGen Consortium} 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 Ayse Demirkan and Peters, {Marjolein J} and Alexander Teumer and {van der Laan}, {Sander W} and Aaron Isaacs and Jouke-Jan Hottenga and Verhulst, {Frank C} and Niek Verweij and Perry, {John R B} and Lisette Stolk and Albert Hofman and Zillikens, {M Carola} and Yongmei Liu and Oostra, {Ben A} and Fernando Rivadeneira and Uitterlinden, {Andr{\'e} G} and {van Duijn}, {Cornelia M} and {Franco Duran}, Oscar and JCM Witteman and {Medina Gomez}, Maria and {Estrada Gil}, Karol and Loos, {Ruth J.F.} and EK Speliotes and {Mattace Raso}, F.U.S. and Visser, {Jenny A.} and {van Meurs}, Joyce and Joop Laven",

year = "2015",

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doi = "10.1038/nature14177",

language = "English",

volume = "518",

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journal = "Nature",

issn = "0028-0836",

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ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, ICBP Consortium, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The GENIE Consortium, The International Endogene Consortium, Locke, AE, Kahali, B, The LifeLines Cohort Study, ReproGen Consortium, 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, Demirkan, A, Peters, MJ, Teumer, A, van der Laan, SW, Isaacs, A, Hottenga, J-J, Verhulst, FC, Verweij, N, Perry, JRB, Stolk, L, Hofman, A, Zillikens, MC, Liu, Y, Oostra, BA, Rivadeneira, F , Uitterlinden, AG, van Duijn, CM, Franco Duran, O, Witteman, JCM, Medina Gomez, M, Estrada Gil, K, Loos, RJF & Speliotes, EK 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 - ADIPOGen Consortium

AU - The AGEN-BMI Working Group

AU - The CARDIOGRAMplusC4D Consortium

AU - The CKDGen Consortium

AU - The GLGC

AU - ICBP Consortium

AU - The MAGIC Investigators

AU - The MuTHER Consortium

AU - The MIGen Consortium

AU - The PAGE Consortium

AU - The GENIE Consortium

AU - The International Endogene Consortium

AU - Locke, Adam E

AU - Kahali, Bratati

AU - The LifeLines Cohort Study

AU - ReproGen Consortium

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 - Demirkan, Ayse

AU - Peters, Marjolein J

AU - Teumer, Alexander

AU - van der Laan, Sander W

AU - Isaacs, Aaron

AU - Hottenga, Jouke-Jan

AU - Verhulst, Frank C

AU - Verweij, Niek

AU - Perry, John R B

AU - Stolk, Lisette

AU - Hofman, Albert

AU - Zillikens, M Carola

AU - Liu, Yongmei

AU - Oostra, Ben A

AU - Rivadeneira, Fernando

AU - Uitterlinden, André G

AU - van Duijn, Cornelia M

AU - Franco Duran, Oscar

AU - Witteman, JCM

AU - Medina Gomez, Maria

AU - Estrada Gil, Karol

AU - Loos, Ruth J.F.

AU - Speliotes, EK

AU - Mattace Raso, F.U.S.

AU - Visser, Jenny A.

AU - van Meurs, Joyce

AU - Laven, Joop

PY - 2015/2/11

Y1 - 2015/2/11

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.

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

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UN SDGs

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