A novel test for recessive contributions to complex diseases implicates Bardet-Biedl syndrome gene BBS10 in idiopathic type 2 diabetes and obesity.

ABSTRACT: Rare-variant association studies in common, complex diseases are customarily conducted under an additive risk model in both single-variant and burden testing. Here, we describe a method to improve detection of rare recessive variants in complex diseases termed RAFT (recessive-allele-frequency-based test). We found that RAFT outperforms existing approaches when the variant influences disease risk in a recessive manner on simulated data. We then applied our method to 1,791 Finnish individuals with type 2 diabetes (T2D) and 2,657 matched control subjects. In BBS10, we discovered a rare variant (c.1189A>G [p.Ile397Val]; rs202042386) that confers risk of T2D in a recessive state (p = 1.38 × 10(-6)) and would be missed by conventional methods. Testing of this variant in an established in vivo ze

SUBMITTER: Lim ET 

PROVIDER: S-EPMC4225638 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature