The low frequency variant rs2229961 causes a valine to isoleucine change at position 134 in exon 4 in the extracellular domain of the receptor. The minor allele principally occurred in European Americans (MAF=0.02) and was rare in African Americans (MAF=0.002). In the primary sample, all 51 individuals with a copy of rs2229961 also possessed at least one copy of the rs16969968 minor (risk) allele, suggesting that these two coding variants are in linkage disequilibrium. Adjusting for the effect of rs16969968, the minor allele of rs2229961 was in the risk direction in European Americans (OR=1.7, p=0.1). Meta-analysis of these primary results and the independent replication samples yielded an OR=1.3 in European Americans (p=0.007) (Supplementary Table S4).
