By performing a large-scale genome-wide survival analysis, we discovered multiple loci associated with AAOS (Table 1). The four genome-wide significantly associated loci, BIN1 (P=7.6×10−13), MS4A (P=5.1×10−11), PICALM (P=4.3×10−14), and APOE (P=1.2×10−67), have been previously reported to be associated with AD risk1. Notably, this is the first study showing that the MS4A locus is associated with AAOS. The most significantly AAOS-associated SNP at this locus, rs7930318, shows a protective effect (HR = 0.93, 95% CI = 0.90–.95) in the survival analysis, consistent with the previous IGAP GWAS logistic regression analysis for AD risk (OR = 0.90, 95% CI = 0.87–.93).
