MRC INTEGRATIVE EPIDEMIOLOGY UNIT (IEU)

SEMINAR SERIES

 Thursday, 25^th January, 2018 : 13,00 – 14.00
Room OS6, Second Floor, Oakfield House

 Andrew Morris
Professor of Statistical Genetics
Department of Biostatistics, University of Liverpool

 Leveraging large-scale genome-wide association studies in diverse populations to advance understanding of the genetic contribution to type 2 diabetes susceptibility

 

Abstract

Genome-wide association studies (GWAS) have identified more than 100 loci contributing to type 2 diabetes (T2D) susceptibility. Historically, these studies have primarily been undertaken in populations of European ancestry. However, with improved coverage of GWAS genotyping arrays and increased population diversity in reference panels for imputation, more recent investigations have been undertaken across a wider range of ethnic groups, including East Asians, South Asians, African Americans and Hispanics/Latinos. The results of these studies have highlighted that the majority of T2D susceptibility loci are shared across ethnic groups, with little evidence of heterogeneity in allelic effects on the disease, suggesting that the underlying causal variants arose prior to human migration out of Africa. Under this model of genetic architecture, we can take advantage of differences in the patterns of linkage disequilibrium between diverse populations to fine-map loci and localise causal variants. To leverage the power of trans-ethnic GWAS for discovery and fine-mapping of T2D susceptibility loci, the DIAMANTE Consortium have brought together the largest collection of genome-wide data in more than 1.1 million individuals (150,000 cases) from diverse populations. Interim analyses of these data identified 42 novel loci for T2D susceptibility at genome-wide significance (p<5x10^-8). Detailed investigation of these loci revealed a complex genetic architecture underlying T2D susceptibility in a 1.5Mb region mapping to INS-IGF2 and KCNQ1, where 15 distinct association signals for the disease were identified. Fine-mapping of these loci highlighted that T2D association signals are enriched in coding sequence, pancreatic islet enhancers and binding sites for NKX2.2 and FOXA2, providing insight into upstream biological mechanisms underlying the disease, and pointing to downstream causal genes through which their effects are mediated.

Biography

Andrew Morris is Professor of Statistical Genetics in the Department of Biostatistics at the University of Liverpool.  His research group focusses on the development and evaluation of novel methodology for the analysis of genome-wide association and sequencing studies of complex human traits.  Some of their recent innovations include approaches for the analysis of rare genetic variation, multiple correlated traits and multi-ethnic studies.  His group play a leading role in analytical groups within international consortia efforts to elucidate the genetic basis of a range of complex human traits, including type 2 diabetes, gestational diabetes, metabolic traits, blood pressure, lung function, kidney function and endometriosis.  He is currently Past President of the International Genetic Epidemiology Society.  

 

ALL WELCOME