Detection of SNP-SNP interactions in trios of parents with schizophrenic children

Schizophrenia (SZ) is a heritable and complex psychiatric disorder with an estimated worldwide prevalence of about 1%. Research on the risk factors for SZ has thus far yielded few clues to causes, but has pointed to a heterogeneous etiology that likely involves multiple genes and gene-environment interactions. In this manuscript, we apply a novel method (trio logic regression, Li et al., 2009) to case-parent trio data from a SZ candidate gene study conducted on families of Ashkenazi Jewish descent, and demonstrate the method's ability to detect multi-gene models for SZ risk in the family-based design. In particular, we demonstrate how this method revealed a genotype-phenotype association that includes an allele without marginal effect. Genet. Epidemiol. 34: 396–406, 2010. © 2010 Wiley-Liss, Inc.