Asscociation of GWAS-linked Loci with Alzheimer's Disease in Han Chinese
Objective: Five genome-wide association studies (GWAS) have recently implicated 9 novel Alzheimer’s disease (AD) susceptibility loci (CLU, CR1, PICALM, BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33 and EPHA1). These studies have been conducted almost exclusively in Caucasian populations and it is unclear whether these observations generalize to populations with different ethnicities. We determined whether these GWAS-linked loci conferred risk for late-onset AD (LOAD) in an independent Northern Han Chinese population.
Methods: We recruited 1, 224 unrelated Northern Han Chinese individuals comprising 612 LOAD patients and 612 healthy controls matched for gender and age. Because CLU, CR1 and PICALM had already been analyzed in the population, we restricted our investigation to analyze the association between 10 SNPs in BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33 and EPHA1 and risk for LOAD.
Results: In the multivariable adjusted analyses, associations with LOAD were successfully replicated for MS4A6A (rs610932; OR=0.632, Bonferroni corrected P = 0.019) and CD33 (rs3865444; OR=1.492, Bonferroni corrected P = 0.017). For BIN1, we observed a positive association in APOE ε4 carriers for rs7561528 under a dominant model, but this did not remain significant after Bonferroni correction. As for ABCA7, CD2AP and EPHA1 SNPs, although similar directional effects observed, there are no significant differences in allele frequency as compared with controls.
Conclusions: This study provides independent support for an association of MS4A and CD33 loci with LOAD risk in the Northern Han Chinese population, and provides the justification for a more in-depth investigation of these regions for possible underlying functional variants.