UNASSIGNED: Waist-to-hip ratio (WHR), a relative comparison of waist and hip circumferences, is an easily accessible measurement of body fat distribution, in particular central abdominal fat. A high WHR indicates more intra-abdominal fat deposition and is an established risk factor for @entity65 and @entity164 2 @entity6 . Recent genome-wide association studies have identified numerous common genetic loci influencing WHR, but the contributions of rare variants have not been previously reported. We investigated rare variant associations with WHR in 1510 European-American and 1186 African-American @entity1 from the National Heart, Lung, and Blood Institute-Exome Sequencing Project. Association analysis was performed on the gene level using several rare variant association methods. The strongest association was observed for rare variants in @entity15955 (P=4.0 * 10(-8)) in European-Americans, where rare variants in this gene are predicted to decrease WHRs. The activation of the @entity15955 gene is involved in inflammatory processes and insulin resistance, which may affect normal food intake and body weight and shape. Meanwhile, aggregation of rare variants in @entity10141 , previously found to harbor common variants associated with WHR and fasting insulin, were nominally associated (P=2.23 * 10(-4)) with higher WHR in European-Americans. However, these significant results are not shared between African-Americans and European-Americans that may be due to differences in the allelic architecture of the two populations and the small sample sizes. Our study indicates that the combined effect of rare variants contribute to the inter-individual variation in fat distribution through the regulation of insulin response.European Journal of @entity1 Genetics advance online publication, 13 January 2016; doi:10.1038/ejhg.2015.272.

Rare variant associations with waist-to-hip ratio in European-American and African-American XXXX from the NHLBI-Exome Sequencing Project.

@entity1 :: ('9606', 'Species') :: ['women', 'Human'] @entity10141 :: ('22837', 'Gene') :: ['COBLL1'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity15955 :: ('3551', 'Gene') :: ['IKBKB'] @entity164 :: ('MESH:D017827', 'Disease') :: ['type'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular disease']
@entity1 :: (9606,Species) :: ['women']
