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

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    URI
    http://hdl.handle.net/11287/618114
    Author
    Locke, A. E. [et al]
    Frayling, Timothy M.
    Hattersley, Andrew T.
    Date
    2015-02
    Journal
    Nature
    Type
    Journal Article
    Meta-Analysis
    Publisher
    Nature
    DOI
    10.1038/nature14177
    Rights
    Archived with permission from Nature.
    Metadata
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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.
    Citation
    Genetic studies of body mass index yield new insights for obesity biology. 2015 Nature. 518(7538):197-206
    Publisher URL
    http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25673413/
    Note
    This article is freely available via PubMed Central. Click on the 'Additional Link' above to access the full-text.
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    • 2015 RD&E publications
    • Diabetes and endocrinology
    • Honorary contracts publications

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