Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians

The regulator of G-protein signaling (RGS) and RGS-like proteins are a diverse family of over 30 molecules that function as GTPase activating proteins for Galpha subunits of the Gq and Gi families of heterotrimeric guanine nucleotide-binding proteins (G proteins). By accelerating GTPase activity, RGS proteins drive G proteins into their inactive GDP-bound forms. G-protein coupled dopamine, metabotropic glutamate, and other neurotransmitter receptors can be modulated by RGS4, the predominant form in brain. The recent finding of decreased RGS4 mRNA expression in post-mortem brains from schizophrenic patients, coupled with the map position of RGS4 to a region previously linked to schizophrenia, as well as other biological data, prompted the investigation of the gene as a disease candidate. Multiple family-based and case-control association studies have been conducted, with modest and conflicting support for particular single nucleotide polymorphism (SNP) markers and SNP marker haplotypes. The present case-control analysis of 568 patients and 689 controls, one of the largest single studies to date, failed to confirm support for association of particular RGS4 SNP alleles, or for association of any particular four, three, or two SNP haplotype.