To further validate the 22 loci with at least suggestive associations to AAOS, we examined their associations with CSF biomarkers, including total tau, phosphorylated tau181, and Aβ42 in a dataset of 3,646 Caucasians extended from our previous report12 (Table 2). Two SNPs showed associations that reached the Bonferroni-corrected threshold (P < 2.27×10−3). Rs4803758 near APOE showed the most significant associations with levels of CSF phosphorylated tau181 (P=3.75×10−4) and CSF Aβ42 (P=3.12×10−5), whereas rs1057233 in the SPI1/CELF1 locus was significantly associated with CSF Aβ42 (P=8.24×10−4). Of note, a SNP adjacent to VLDLR, rs7867518, showed the most significant association with CSF total tau (P=3.02×10−3), but failed to pass the Bonferroni-corrected threshold. The protective and deleterious effects in the survival analysis of these three SNPs were concordant with directionalities of their CSF biomarker associations; for example, the protective rs1057233G allele was associated with higher CSF Aβ42 levels and the risk rs1057233A allele was associated with lower CSF Aβ42 levels.
