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

AE Locke; B Kahali; MAGIC Collaboration; SI Berndt; AE Justice; TH Pers; R Felix; C Powell; S Vedantam; ML Buchkovich; Jiaqi Yang; DC Croteau-Chonka; T Esko; T Fall; T Ferreira; S Gustafsson; Z Kutalik; JA Luan; R Magi; JC Randall; TW Winkler; AR Wood; T Workalemahu; JD Faul; Najaf Amin; M Beekman; Ayse Demirkan; K (Kirsten) Fischer; Maria Medina Gomez; Marjolein Peters; S Trompet; Sander Laan; Aaron Isaacs; Karol Estrada Gil; JJ (Jouke Jan) Hottenga; IM (Ilja) Nolte; Frank Verhulst; N (Niek) Verweij; Lisette Stolk; AC Heath; OH Franco Duran; Bert Hofman; AJ (A.) Oldehinkel; RP (Ronald) Stolk; JCM Witteman; M.C. Zillikens; Ben Oostra; Fernando Rivadeneira; TD Spector; André Uitterlinden; Ruth J.F. Loos; K Speliotes

doi:10.1038/nature14177

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

AE Locke, B Kahali, MAGIC Collaboration, SI Berndt, AE Justice, TH Pers, R Felix, C Powell, S Vedantam, ML Buchkovich, Jiaqi Yang, DC Croteau-Chonka, T Esko, T Fall, T Ferreira, S Gustafsson, Z Kutalik, JA Luan, R Magi, JC RandallTW Winkler, AR Wood, T Workalemahu, JD Faul, Najaf Amin, M Beekman, Ayse Demirkan, K (Kirsten) Fischer, Maria Medina Gomez, Marjolein Peters, S Trompet, Sander Laan, Aaron Isaacs, Karol Estrada Gil, JJ (Jouke Jan) Hottenga, IM (Ilja) Nolte, Frank Verhulst, N (Niek) Verweij, Lisette Stolk, AC Heath, OH Franco Duran, Bert Hofman, AJ (A.) Oldehinkel, RP (Ronald) Stolk, JCM Witteman, M.C. Zillikens, Ben Oostra, Fernando Rivadeneira, TD Spector, André Uitterlinden, Ruth J.F. Loos, K Speliotes

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

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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 ∼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)	197-206
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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Locke, AE., Kahali, B., MAGIC Collaboration, Berndt, SI., Justice, AE., Pers, TH., Felix, R., Powell, C., Vedantam, S., Buchkovich, ML., Yang, J., Croteau-Chonka, DC., Esko, T., Fall, T., Ferreira, T., Gustafsson, S., Kutalik, Z., Luan, JA., Magi, R., ... Speliotes, K. (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{34743e29cda046788bf2087bff1ac636,

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 ∼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.",

author = "AE Locke and B Kahali and {MAGIC Collaboration} and SI Berndt and AE Justice and TH Pers and R Felix and C Powell and S Vedantam and ML Buchkovich and Jiaqi Yang and DC Croteau-Chonka and T Esko and T Fall and T Ferreira and S Gustafsson and Z Kutalik and JA Luan and R Magi and JC Randall and TW Winkler and AR Wood and T Workalemahu and JD Faul and Najaf Amin and M Beekman and Ayse Demirkan and Fischer, {K (Kirsten)} and {Medina Gomez}, Maria and Marjolein Peters and S Trompet and Sander Laan and Aaron Isaacs and {Estrada Gil}, Karol and Hottenga, {JJ (Jouke Jan)} and Nolte, {IM (Ilja)} and Frank Verhulst and Verweij, {N (Niek)} and Lisette Stolk and AC Heath and {Franco Duran}, OH and Bert Hofman and Oldehinkel, {AJ (A.)} and Stolk, {RP (Ronald)} and JCM Witteman and M.C. Zillikens and Ben Oostra and Fernando Rivadeneira and TD Spector and Andr{\'e} Uitterlinden and {Mattace Raso}, F.U.S. and Loos, {Ruth J.F.} and K Speliotes",

year = "2015",

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day = "11",

doi = "10.1038/nature14177",

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Locke, AE, Kahali, B, MAGIC Collaboration, Berndt, SI, Justice, AE, Pers, TH, Felix, R, Powell, C, Vedantam, S, Buchkovich, ML, Yang, J, Croteau-Chonka, DC, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, JA, Magi, R, Randall, JC, Winkler, TW, Wood, AR, Workalemahu, T, Faul, JD, Amin, N, Beekman, M, Demirkan, A, Fischer, K, Medina Gomez, M, Peters, M, Trompet, S, Laan, S, Isaacs, A, Estrada Gil, K, Hottenga, JJ, Nolte, IM, Verhulst, F, Verweij, N, Stolk, L, Heath, AC, Franco Duran, OH, Hofman, B, Oldehinkel, AJ, Stolk, RP, Witteman, JCM, Zillikens, MC, Oostra, B, Rivadeneira, F, Spector, TD, Uitterlinden, A, Loos, RJF & Speliotes, K 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, AE

AU - Kahali, B

AU - MAGIC Collaboration

AU - Berndt, SI

AU - Justice, AE

AU - Pers, TH

AU - Felix, R

AU - Powell, C

AU - Vedantam, S

AU - Buchkovich, ML

AU - Yang, Jiaqi

AU - Croteau-Chonka, DC

AU - Esko, T

AU - Fall, T

AU - Ferreira, T

AU - Gustafsson, S

AU - Kutalik, Z

AU - Luan, JA

AU - Magi, R

AU - Randall, JC

AU - Winkler, TW

AU - Wood, AR

AU - Workalemahu, T

AU - Faul, JD

AU - Amin, Najaf

AU - Beekman, M

AU - Demirkan, Ayse

AU - Fischer, K (Kirsten)

AU - Medina Gomez, Maria

AU - Peters, Marjolein

AU - Trompet, S

AU - Laan, Sander

AU - Isaacs, Aaron

AU - Estrada Gil, Karol

AU - Hottenga, JJ (Jouke Jan)

AU - Nolte, IM (Ilja)

AU - Verhulst, Frank

AU - Verweij, N (Niek)

AU - Stolk, Lisette

AU - Heath, AC

AU - Franco Duran, OH

AU - Hofman, Bert

AU - Oldehinkel, AJ (A.)

AU - Stolk, RP (Ronald)

AU - Witteman, JCM

AU - Zillikens, M.C.

AU - Oostra, Ben

AU - Rivadeneira, Fernando

AU - Spector, TD

AU - Uitterlinden, André

AU - Mattace Raso, F.U.S.

AU - Loos, Ruth J.F.

AU - Speliotes, K

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 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 ∼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 ∼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.

U2 - 10.1038/nature14177

DO - 10.1038/nature14177

M3 - Article

VL - 518

SP - 197

EP - 206

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7538

ER -

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

Abstract

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