Combining the scan and replication data, only rs10513025 met criteria for genome-wide significance defined by LD and permutation analyses (P < 2.5 × 10−7). To increase coverage of this region and fill in missing genotypes and SNPs that failed quality control, we performed imputation analysis. rs10513026 was highly (but not perfectly) correlated to the replicated chromosome 5 SNP (rs10513025) and showed even stronger association than originally observed with rs10513025 (Supplementary Figure 3). These and several other promising SNPs were directly genotyped in the original scan samples and, in fact, showed higher levels of significance (Table 2). Direct genotyping confirmed that rs10513026 showed stronger association than rs10513025 (P-value 4.5 × 10−6 vs. 9.8 × 10−6 in the re-genotyped scan trios), increasing the significance of this observation further. Several other promising results from this analysis were genotyped in a subset of scan samples, and, of note, the top SNP in imputation analysis (rs10874241, imputation P = 9.8 × 10−7, OR = 0.43) showed consistent results (OR = 0.4, P = 4 × 10−7) when directly genotyped (Supplementary Table 4).
