Give GWAS a Chance

摘要

From 2007 to 2015, genome-wide association studies (GWAS) resulted in the discovery of over 260 genetic loci associated with obesity and type 2 diabetes (T2D) (1,2). Although GWAS have validated "old culprits" (e.g., PPARG, KCNJ11), illuminated novel disease-causing biological pathways (e.g., the zinc transporter SLC30A8), and have led to quick trans-lational medicine applications (e.g., hs-CRP as a diagnostic tool for HNF1A maturity-onset diabetes of the young) (3-5), some have questioned their utility (6,7). They argue GWAS are expensive and that GWAS-derived single nucle-otide polymorphisms (SNPs) explain only a fraction of the heritability for complex traits (6,7). They propose to focus instead on next-generation sequencing (NGS) studies or post-GWAS experiments (functional studies, animal models, clinical studies) (6,7). This debate has led to skepticism about the benefits of GWAS and hesitancy to fund additional GWAS. With the ever-decreasing costs in NGS technologies, we should seriously address the relevance of funding more GWAS. In this issue of Diabetes, Scott et al. (8) provide some elements of response to this important question.