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Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Original publication

DOI

10.1038/ng.2606

Type

Journal article

Journal

Nature genetics

Publication Date

05/2013

Volume

45

Pages

501 - 512

Addresses

US Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.

Keywords

Humans, Obesity, Genetic Predisposition to Disease, Anthropometry, Body Mass Index, Body Height, Waist-Hip Ratio, Case-Control Studies, Genotype, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, European Continental Ancestry Group, Meta-Analysis as Topic, Genome-Wide Association Study