Abstract
Based on an Ashkenazy Jewish case-control cohort for schizophrenia, we carried out (1) genetic association analysis for one variant at a time (GWAS) and (2) digenic analysis by comparing frequencies of genotype pairs between cases and controls. To control for genetic heterogeneity between sexes, we analyzed males and females separately. After pruning of variants in each of males and females, single-variant allelic analysis furnished 9 and 8 statistically significant variants in males and females, respectively, with 3 of these variants being significant in both males and females. Of the 14 distinct variants in males and females, 5 (36%) reside in genes. For digenic analysis, we evaluated all pairs of variants and, for a given variant pair, all nine genotype pairs. For each genotype pair, we applied the Fisher exact test to evaluate whether the given genotype pair was more frequent in cases than controls. We found 76 significant genotype pairs, comprising 36 distinct variants, 20 (56%) of which reside in genes, with many of which being known risk genes, thus lending credence to our approach.