All 12 potential secondary signals at loci previously reported by den Hoed et al. (12) were genome-wide significant in the combined meta-analysis (Supplementary Material, Table S2) and are independent to the known SNPs according to LD (r2 < 0.2). We performed a conditional analysis using Genome-wide Complex Traits Analysis (GCTA) to formally identify secondary signals of association. Five of the 12 validated potential secondary SNVs (within CD46, CCDC141, SLC35F1, ACHE and KIAA1755 loci) were selected within the final GCTA model (Supplementary Material, Table S3). At four of the previously reported HR regions the secondary signals that we identified were confirmed to be statistically independent signals of association: CD46 (rs2745967), CCDC141 (rs10497529), SLC35F1 (rs12210810) and KIAA1755 (rs41282820) in addition to the known SNV, as both the published SNV and the new secondary SNV were present in the final GCTA model of jointly independent associated variants. Hence, we identified two distinct signals of association at each of these four known HR loci. However, the published SNV at the ACHE locus (rs13245899) is not covered on the Exome Chip, or by any proxies
