Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity

• Published in: Nature genetics Vol. 41; no. 1; pp. 18 - 24
• Main Authors: Thorleifsson, Gudmar, Walters, G Bragi, Gudbjartsson, Daniel F, Steinthorsdottir, Valgerdur, Sulem, Patrick, Helgadottir, Anna, Styrkarsdottir, Unnur, Gretarsdottir, Solveig, Thorlacius, Steinunn, Jonsdottir, Ingileif, Jonsdottir, Thorbjorg, Olafsdottir, Elinborg J, Olafsdottir, Gudridur H, Jonsson, Thorvaldur, Jonsson, Frosti, Borch-Johnsen, Knut, Hansen, Torben, Andersen, Gitte, Jorgensen, Torben, Lauritzen, Torsten, Aben, Katja K, Verbeek, André LM, Roeleveld, Nel, Kampman, Ellen, Yanek, Lisa R, Becker, Lewis C, Tryggvadottir, Laufey, Rafnar, Thorunn, Becker, Diane M, Gulcher, Jeffrey, Kiemeney, Lambertus A, Pedersen, Oluf, Kong, Augustine, Thorsteinsdottir, Unnur, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2009; Nature Publishing Group
• Subjects: Agriculture; alpha gene; Animal Genetics and Genomics; Base Sequence; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Body Mass Index; Body Weight - genetics; Cancer Research; Complications and side effects; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Environmental factors; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Gene Function; Genetic aspects; Genetic Predisposition to Disease; genetic-variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human - genetics; Genome-Wide Association Study; Health aspects; Human Genetics; Humans; Medical research; Medical sciences; metaanalysis; Metabolic diseases; metabolic syndrome; Minority & ethnic groups; neurite outgrowth; Obesity; Obesity - complications; Obesity - genetics; overweight; Physiological aspects; polymorphism; Polymorphism, Single Nucleotide - genetics; protein; Quality control; Quantitative Trait Loci - genetics; Quantitative Trait, Heritable; Risk factors; Single nucleotide polymorphisms; weight; Denmark; Iceland; Variant; Obesity; Association; Nutrition disorder; Yield; Locus; Nutritional status
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.274

Gudmar Thorleifsson and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Joel Hirschhorn and colleagues. Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 × 10 −7 . This includes previously identified variants close to or in the FTO , MC4R , BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.