UCL Genetics Institute


BCGES seminar - Tuesday 6 August at 4:30pm

22 July 2013

The next BCGES will be on Tuesday 6 August in UCL Darwin B15 (Biochemistry LT):

Title: Discovery and fine-mapping of type 2 diabetes (T2D) susceptibility loci via trans-ethnic meta-analysis.

Speaker: Andrew Morris (Wellcome Trust Centre for Human Genetics, Oxford)


The majority of genome-wide association studies (GWAS) of T2D susceptibility have been undertaken in populations of European ancestry, which contain only a subset of human genetic variation, and thus are insufficient to fully characterise risk variants in other ethnic groups.  More recent T2D GWAS have been performed, with great success, in populations from other ancestry groups, including East Asians, South Asians, Mexicans and Mexican Americans, and African Americans.  These studies have provided initial evidence of overlap in T2D susceptibility loci across ancestry groups and coincident risk alleles at lead SNPs between diverse populations.  Consequently, we would expect to improve power to detect novel susceptibility loci for the disease and enhance fine-mapping resolution of causal variants by combining GWAS across ancestry groups through trans-ethnic meta-analysis because of increased sample size and differences in the structure of linkage disequilibrium (LD) between such diverse populations.

In this seminar, I will present the results of a large-scale trans-ethnic meta-analysis of T2D GWAS from populations of European, East Asian, South Asian, and Mexican and Mexican American ancestry, in a total of 26,488 cases and 83,964 controls, and discuss the novel insights they have provided into the underlying genetic architecture of the disease.  I will also present methodology for trans-ethnic fine-mapping that takes account of differences in patterns of LD between diverse populations, and demonstrate the utility of this approach in localising causal variants at five established T2D susceptibility loci by combining GWAS in 21,997 cases and 42,730 controls from populations of European, East Asian, South Asian, Hispanic American and African American ancestry.