A single novel SNP on chromosome 3, rs7644567, also reached GWS in the meta-analysis (z = 5.68, p = 1.36E-8; Supplementary Figure S4). Potential biological associations with rs7644567, including chromatin contacts (Supplementary Figure S5) and cerebellar expression of RBMS3, are summarized in Supplementary Information A9. However, rs7644567 did not replicate in two independent AA samples (Yale-Penn2 and COGA AAfGWAS) or the independent FINRISK cohort; all three replication cohorts estimating effects of the minor allele in the opposite direction of the discovery meta-analysis (Supplementary Table S4). The SNP is also rare in most EU samples (minor allele frequency [MAF] < 0.01), with the current GWAS results primarily attributable to AA cohorts, along with FinnTwin and NAG-Fin. The EU cohorts in the discovery meta-analysis show no evidence of association of AD with the SNPs in strongest LD with rs7644567 in African (rs13098461; z = 0.27, p = 0.79) or Finnish (rs9854300; z = 0.10, p = 0.92) reference samples (Supplementary Information A9). Based on the clear lack of replication there is insufficient evidence to conclude rs7644567 is associated with AD based on the current results.
