We restricted our effect size estimates (Table 2, Supplementary Table 2) to the Stage 2 replication samples (up to N=76,558) to avoid inflation introduced by the discovery cohorts (“winner’s curse”26). The previously identified loci G6PC2, MTNR1B and GCK showed the largest effects on FG (0.075, 0.067 and 0.062 mmol/L per allele, respectively), with the remaining loci showing smaller effects (0.008 to 0.030 mmol/L per allele, Table 2). The proportion of variance in FG explained by the 14 FG loci with replication data (i.e. all FG loci except for TCF7L2 and SLC30A8) ranged from 3.2–4.4% in six replication studies providing this information. Because results from our largest unselected community-based cohort (Framingham) were on the lower bound of these estimates (3.2%), we felt reassured that the winner’s curse is not a major concern in this instance, and selected it to estimate the proportion of heritability explained and the genotype score. With a heritability estimate of 30.4% in Framingham, these 14 loci explain a substantial proportion (~10%) of the inherited variation in FG. If these same loci harbor additional independent variants (e.g. those
