Fine mapping of type 2 diabetes susceptibility loci

Curr Diab Rep. 2014;14(11):549. doi: 10.1007/s11892-014-0549-2.

Abstract

Genome-wide association studies of type 2 diabetes have been extremely successful in discovering loci that contribute genetic effects to susceptibility to the disease. However, at the vast majority of these loci, the variants and transcripts through which these effects on type 2 diabetes are mediated are unknown, limiting progress in defining the pathophysiological basis of the disease. In this review, we will describe available approaches for assaying genetic variation across loci and discuss statistical methods to determine the most likely causal variants in the region. We will consider the utility of trans-ethnic meta-analysis for fine mapping by leveraging the differences in the structure of linkage disequilibrium between diverse populations. Finally, we will discuss progress in fine-mapping type 2 diabetes susceptibility loci to date and consider the prospects for future efforts to localise causal variants for the disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide*

Substances

  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human