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Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Original publication

DOI

10.1038/ng.287

Type

Journal article

Journal

Nature genetics

Publication Date

01/2009

Volume

41

Pages

25 - 34

Addresses

Genetic Investigation of ANthropometric Traits Consortium.

Keywords

Wellcome Trust Case Control Consortium, Genetic Investigation of ANthropometric Traits Consortium, Central Nervous System, Humans, Obesity, Genetic Predisposition to Disease, Body Weight, Anthropometry, Body Mass Index, Cohort Studies, Gene Dosage, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Alleles, Quantitative Trait Loci, Meta-Analysis as Topic, Genome-Wide Association Study