Shifman and colleagues conducted a genome-wide association study for schizophrenia using a novel DNA pooling strategy71. One hundred ninety four SNPs were selecting for further studies based on their ranking and statistical significance in the studies in pooled DNA, and their biological plausibility71. These SNPs were then individually typed in 745 patients and 759 controls from the Ashkenazi Jewish population. The smallest P-value corresponded to SNP rs7341475 (G→A), for which the frequency of the GG genotype was 0.76 in female patients compared to 0.59 in female controls (P = 9.8 × 10−5). There was no association in males (P = 0.47), yielding a significant genotype-sex interaction (P = 0.0053) (Table 2). This SNP is located on chromosome 7 in intron 4 of the Reelin gene (RELN), which had previously been studied as a candidate for schizophrenia or related phenotypes (Ref72 and references therein). In the Ashkenazi Jewish sample, rs7341475 showed high linkage disequilibrium (LD) with other SNPs in the third and fourth intron of the RELN gene, but the LD did not extend to neighboring genes, suggesting that the association with schizophrenia is with variation in the RELN gene.
