Prioritising Causal Genes at Type 2 Diabetes Risk Loci.
Grotz AK., Gloyn AL., Thomsen SK.
PURPOSE OF REVIEW: Genome-wide association studies (GWAS) for type 2 diabetes (T2D) risk have identified a large number of genetic loci associated with disease susceptibility. However, progress moving from association signals through causal genes to functional understanding has so far been slow, hindering clinical translation. This review discusses the benefits and limitations of emerging, unbiased approaches for prioritising causal genes at T2D risk loci. RECENT FINDINGS: Candidate causal genes can be identified by a number of different strategies that rely on genetic data, genomic annotations, and functional screening of selected genes. To overcome the limitations of each particular method, integration of multiple data sets is proving essential for establishing confidence in the prioritised genes. Previous studies have also highlighted the need to support these efforts through identification of causal variants and disease-relevant tissues. Prioritisation of causal genes at T2D risk loci by integrating complementary lines of evidence promises to accelerate our understanding of disease pathology and promote translation into new therapeutics.