The field of human genetics has witnessed tremendous acceleration in the last decade, driven in part by the advent of genome-wide association studies (GWAS) (1,2). However, novel insights have not kept pace. In most cases, the specific DNA sequences that cause the molecular changes leading to type 2 diabetes (T2D) have not been identified, and robust signals of association are often initially opaque with regard to a plausible functional mechanism (3,4). Thus, although GWAS constitute a powerful approach to rapidly and systematically uncover associations that may open new windows into T2D pathophysiology, they do not circumvent the need to refine the associated loci to find the precise "causal" DNA sequences-causal in the sense that altering these sequences would eliminate the clinical phenotype (5,6).
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