title: Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
abstract: 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.
authors.affiliation: US Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
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authors.lastname: Heid
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authors.lastname: Karpe
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authors.lastname: O'Connell
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authors.lastname: Pawitan
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authors.initials: EE
authors.lastname: Schadt
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authors.initials: D
authors.lastname: Schlessinger
authors.forename: Valgerdur
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authors.lastname: Steinthorsdottir
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authors.initials: JN
authors.lastname: Hirschhorn
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authors.initials: CM
authors.lastname: Lindgren
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authors.initials: AP
authors.lastname: Morris
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authors.lastname: Meyre
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authors.lastname: Scherag
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authors.initials: MI
authors.lastname: McCarthy
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authors.initials: EK
authors.lastname: Speliotes
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authors.initials: KE
authors.lastname: North
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authors.lastname: Loos
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authors.initials: E
authors.lastname: Ingelsson
mesh_terms: D000886:Anthropometry; D001827:Body Height / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci; D049629:Waist-Hip Ratio; D044465:White People / Q000235:genetics
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