Inverse variance weighted meta-analyses revealed 12 independent loci associated with FG and/or HOMA-B at genome-wide significance levels (Table 1, Supplementary Table 2, Supplementary Figure 2a–b). These included five novel associations for loci in or near ADCY5, MADD, ADRA2A, CRY2 and FADS1 (Table 1, Figure 1a–j); four previously reported FG-associated loci in or near GCK, GCKR, G6PC2, and MTNR1B; the recently reported DGKB/TMEM19524; and two loci in T2D susceptibility genes TCF7L2 (rs4506565, r2=0.92 with the previously reported SNP rs7903146) and SLC30A8 (rs11558471, r2=0.96 with the previously reported SNP rs13266634). Seven additional loci had reproducible evidence for association with FG and/or HOMA-B across studies at the arbitrary summary threshold of P<2×10−5 chosen to prioritize SNPs for follow-up (Table 1, Supplementary Table 2). After excluding SNPs within the four previously genome-wide significant FG loci GCK, GCKR, G6PC2 and MTNR1B, we still observed an excess of small P-values compared to a distribution expected under the null hypothesis (Figure 2a–b), suggesting that some of these additional loci are likely to represent novel FG and/or HOMA-B loci that merit additional investigation.
