Identification of genetic variants underlying coronary artery disease and associated phenotypes in Indian Asians. (360G-Wellcome-084723_Z_08_Z)

The primary objective of this study is to identify novel genetic variants underlying coronary artery disease in Indian Asians. We have already assembled a collection of Indian Asians with coronary artery disease, and population- based controls in West London. In stage one, we will carry out a Genome-Wide Association (GWA) study of 4000 coronary artery disease cases and 4000 common controls (age/sex stratified and free from coronary disease, obesity, diabetes, hypertension). This offers 86% power to detect a risk ratio of 1.2 (additive model) at MAF 20%, P<10-4. In stage two, we will replicate the ~100 top-ranking SNPs in a further 4000 Indian Asian coronary artery disease cases and 4000 controls. In stage three (no funding requested) SNPs showing equivocal association with coronary artery disease in stage two will be genotyped in a further 6000 Indian Asian cases and 6000 controls. Our secondary objective is to integrate the above GWA data on 4000 coronary artery disease cases, with our existing GWA data on 5618 Indian Asians, to yield GWA data on 3782 persons with obesity, 3341 with type 2 diabetes, and 4164 with hypertension, for comparison against the 4000 Indian Asian common controls for each phenotype. In order to identify novel genetic variants underlying obesity and hypertension, we will replicate ~100 top-ranking SNPs for each of these phenotypes in 4000 obese, and 4000 HT Indian Asian cases, and 4000 controls respectively. Replication of type 2 diabetes associations is not included in the current proposal, as it is the subject of an application to the MRC (October 2007 board meeting). We also have access to large European cohorts (such as MORGAM, ENGAGE and CARDIOGENICS) for evaluation amongst Europeans of the SNPs replicated in Indian Asians, to identify Indian Asian specific and shared variants. This research will lead to the creation of an Indian Asian WTCCC , focused on the identification of genetic variants underlying coronary artery disease, and its associated phenotypes of obesity, diabetes and hypertension in Indian Asians. As an additional outcome of this research, we will generate whole-genome data for 4000 Indian Asian controls, which will be available as a unique resource for future genetic studies in Indian Asians.