Type 1 diabetes genome-wide association studies: not to be lost in translation

摘要

Genetic studies have identified >60 loci associated with the risk of developing type 1 diabetes (T1D). The vast majority of these are identified by genome-wide association studies (GWAS) using large case–control cohorts of European ancestry. More than 80% of the heritability of T1D can be explained by GWAS data in this population group. However, with few exceptions, their individual contribution to T1D risk is low and understanding their function in disease biology remains a huge challenge. GWAS on its own does not inform us in detail on disease mechanisms, but the combination of GWAS data with other omics-data is beginning to advance our understanding of T1D etiology and pathogenesis. Current knowledge supports the notion that genetic variation in both pancreatic β cells and in immune cells is central in mediating T1D risk. Advances, perspectives and limitations of GWAS are discussed in this review.