What have we learned from six years of GWAS in autoimmune diseases, and what is next?

Abstract

Genome-wide association studies (GWAS) have discovered hundreds of common genetic variants that predispose humans to autoimmune diseases, opening up unprecedented potential for elucidating the pathways and processes of disease. To understand the role of these variants in susceptibility, we need to derive mechanistic insight by integration of genetic results with other biological data types and also with careful functional studies. In many cases, such studies have highlighted coherent biological processes at a high level and elucidated specific mechanisms that contribute to autoimmunity and inflammation. The understanding of the genetic component of autoimmune etiology will become more complete as fine-mapping and sequencing data become readily available. A comprehensive catalog of human immune phenotypes could provide a functional basis for assessing genetic influence on immune function and variation in response to therapeutic interventions, as well as for rationally designing new targeted therapeutics.