Exome localization of complex disease association signals

BMC Genomics. 2011 Feb 1:12:92. doi: 10.1186/1471-2164-12-92.

Abstract

Background: Genome-wide association studies (GWAS) of common diseases have had a tremendous impact on genetic research over the last five years; the field is now moving from microarray-based technology towards next-generation sequencing. To evaluate the potential of association studies for complex diseases based on exome sequencing we analysed the distribution of association signal with respect to protein-coding genes based on GWAS data for seven diseases from the Wellcome Trust Case Control Consortium.

Results: We find significant concentration of association signal in exons and genes for Crohn's Disease, Type 1 Diabetes and Bipolar Disorder, but also observe enrichment from up to 40 kilobases upstream to 40 kilobases downstream of protein-coding genes for Crohn's Disease and Type 1 Diabetes; the exact extent of the distribution is disease dependent.

Conclusions: Our work suggests that exome sequencing may be a feasible approach to find genetic variation associated with complex disease. Extending the exome sequencing to include flanking regions therefore promises further improvement of covering disease-relevant variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder / genetics
  • Crohn Disease / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Exons*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide