Schizophrenia is a highly heritable neuropsychiatric condition that affects millions of individuals in the U.S. alone. Recent analyses of structural genetic variation have identified and rapidly confirmed a number of rare variants contributing to this disorder. Surprisingly, the same rare genetic contributors have often been found to be risk factors for multiple neuropsychiatric conditions, including autism, mental retardation, and epilepsy. This suggests that these rare variants may confer a "neuropsychiatric vulnerability" and that the ultimate clinical manifestation depends on other genetic or environmental influences. This study further investigates the gene-environment basis of neuropsychiatric diseases by performing whole-genome sequencing in 100 schizophrenia patients to search for rare, highly penetrant associated genetic variants. Potentially associated genetic markers will be genotyped in affected and unaffected family members to determine their specificity for schizophrenia versus other neuropsychiatric conditions and to investigate genetic and environmental modifiers of their effects. This work could elucidate the molecular basis of schizophrenia, as well as other neuropsychiatric conditions like autism, and potentially indicate novel targets for psychiatric drugs.