Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia

Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.