Complex segregation analysis provides compelling evidence for a major geneunderlying obsessive-compulsive disorder and for heterogeneity by sex

Evidence from twin and family studies supports a genetic etiology for obses sive-compulsive disorder (OCD). The purpose of this study was to test wheth er a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a majo r gene. A Mendelian-dominant model, with significant sex effects and with r esidual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogen eity with respect to familial aggregation. Segregation analyses of 86 famil ies with a female proband and of the 67 families with a male proband sugges ted that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups .