rs1160985

This case-control study attempted to replicate the association of TOMM40 polyT polymorphism (rs10524523) with Alzheimer's disease risk and age at onset. In a large series of 1594 LOAD cases and 1190 controls, the study failed to replicate the previously reported association with age at onset but found a significant association between rs10524523 and risk for LOAD among APOE 33 homozygotes in the opposite direction (OR=0.78, 95% CI=0.65-0.95; p=0.004, allele frequencies 0.41 vs 0.48 in cases vs controls). No association was found between rs10524523 and CSF biomarker levels (tau, phosphorylated tau, Aβ42) or TOMM40/APOE gene expression.

This comprehensive genome-wide association study examined genetic variants contributing to late-onset Alzheimer's disease (AD) in 513 African American cases and 496 controls, plus replication in 5 white cohorts. The APOE ε4 allele showed strong association (P=9.69×10⁻²³), and after adjusting for APOE, rs6859 in PVRL2 remained significantly associated (P=0.0087). The study found associations with variants in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, though effect directions sometimes differed from white populations. Novel associations with suggestive evidence were identified in PROX1, CNTNAP2, STK24, and other genes, though not replicated in whites.