Nine of the 12 previously unknown variants were validated based on exome-wide significance (P ≤ 2.12 × 10−7) in the combined meta-analysis of CHARGE and UK Biobank data, and on Bonferroni-adjusted significance (P ≤ 0.0042 for 12 tests) in the replication dataset alone, with concordant directions of effects taking into account the inverse relationship between the RR-interval from the discovery data and HR from the replication data (Table 1; Fig. 2). Indeed, all nine SNV associations were genome-wide significant in the combined meta-analysis (P < 5.0 × 10−8). Four of our nine validated novel loci were reported in a UK Biobank study (17) that was published after completion of our study (Table 1B). Hence, we present results here for five unreported novel loci (Table 1A;Supplementary Material, Figs S5 and S6).
