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

LifeLines Cohort Study; ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium

doi:10.1038/nature14177

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

LifeLines Cohort Study, ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium

GPI

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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 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 (US)
Pages (from-to)	197-206
Number of pages	10
Journal	Nature
Volume	518
Issue number	7538
DOIs	https://doi.org/10.1038/nature14177
State	Published - Feb 12 2015

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UN SDGs

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

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10.1038/nature14177

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LifeLines Cohort Study, & ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-206. https://doi.org/10.1038/nature14177

Genetic studies of body mass index yield new insights for obesity biology. / LifeLines Cohort Study; ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium.
In: Nature, Vol. 518, No. 7538, 12.02.2015, p. 197-206.

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

LifeLines Cohort Study & ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium 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

LifeLines Cohort Study, ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177

LifeLines Cohort Study ; ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium. / Genetic studies of body mass index yield new insights for obesity biology. In: Nature. 2015 ; Vol. 518, No. 7538. pp. 197-206.

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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 = "\{LifeLines Cohort Study\} and \{ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium\} and Locke, \{A. E.\} and B. Kahali and Berndt, \{S. I.\} and Justice, \{A. E.\} and Pers, \{T. H.\} and Day, \{F. R.\} and C. Powell and S. Vedantam and Buchkovich, \{M. L.\} and J. Yang and Croteau-Chonka, \{D. C.\} and T. Esko and T. Fall and T. Ferreira and S. Gustafsson and Z. Kutalik and J. Luan and R. M{\"a}gi and Randall, \{J. C.\} and Winkler, \{T. W.\} and Wood, \{A. R.\} and T. Workalemahu and Faul, \{J. D.\} and Smith, \{J. A.\} and Zhao, \{J. H.\} and W. Zhao and J. Chen and R. Fehrmann and K. Hedman and J. Karjalainen and Schmidt, \{E. M.\} and D. Absher and N. Amin and D. Anderson and M. Beekman and Bolton, \{J. L.\} and Bragg-Gresham, \{J. L.\} and S. Buyske and A. Demirkan and G. Deng and Ehret, \{G. B.\} and B. Feenstra and Feitosa, \{M. F.\} and K. Fischer and A. Goel and J. Gong and Jackson, \{A. U.\} and S. Kanoni and Kleber, \{M. E.\} and Yanbin Dong",

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AU - ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium

AU - Locke, A. E.

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AU - Ferreira, T.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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