These individuals with the highest GRSs differed significantly from all other individuals with T2D (Fig 1C, S7, and S9 Tables); for instance, compared to all individuals across the three studies with T2D, those with extreme GRS in the Beta Cell cluster (N = 1,068) had decreased BMI, HC, and WC (P < 10−3) and percent body fat (P < 0.05), with a trend toward decreased fasting C-peptide (P = 0.19), and those in the Proinsulin cluster (N = 1,117) had significantly decreased fasting C-peptide levels (P = 0.003). Here, INS is linked to type 2 diabetes mellitus.