Univariate and Bivariate Linkage Analysis Identifies Pleiotropic Loci Underlying Lipid Levels and Type 2 Diabetes Risk

Dyslipidemia frequently co-occurs with type 2 diabetes (T2D) and with obesity. To investigate whether the co-occurrence is due to pleiotropic genes, we performed univariate linkage analysis of lipid levels and bivariate linkage analysis of pairs of lipid levels and of lipid levels paired with T2D, body mass index (BMI), and waist-hip ratio (WHR) in the African American subset of the Genetics of NIDDM (GENNID) sample. We obtained significant evidence for a pleiotropic low density lipoprotein cholesterol (LDL-C)-T2D locus on chromosome 1 at 16-19 megabases (MB) (bivariate lod = 4.41), as well as a non-pleiotropic triglyceride (TG) locus on chromosome 20 at 28-34 MB (univariate lod = 3.57). In addition, near-significant evidence supported TG-T2D loci on chromosome 2 at 81-101 MB (bivariate lod = 4.23) and 232-239 MB (bivariate lod = 4.27) and on chromosome 7 at 147-151 MB (univariate lod = 3.08 for TG with P = 0.041 supporting pleiotropy with T2D), as well as an LDL-C-BMI locus on chromosome 3 at 137-147 MB (bivariate lod score = 4.25). These findings provide evidence that at least some of the co-occurrence of dyslipidemia with T2D and obesity is due to common underlying genes.