Dopamine gene variants and schizophrenia: A scheme for investigating nominally significant or discrepant associations
Introduction Environmentalists and geneticists alike agree that a unitary causation for schizophrenia (SZ) is unlikely (Gottesman, 1994; Jablensky & Kalaydjieva, 2003). The attraction of gene-mapping studies is the prospect of invoking causation through associations, in contrast to classical epidemiological studies. Recent schizophrenia gene-mapping efforts have identified several putative risk variants, but they have not been replicated widely. The main obstacle is the relatively modest risk conferred by individual variants (odds ratios, OR, ~ 1.21.5), making replication difficult. Though larger effects have been reported with some rare variants, the precise risk variants are unknown and many await replication. Additional variants with larger effects may not be detected. Thus, it may be difficult to fulfill classical criteria for causation. These problems are shared with other common, genetically complex disorders.