Association of GWAS and candidate gene loci of dopaminergic system with major depression, schizophrenia and bipolar disorder in the Pakistani population

Abstract

The dopaminergic pathways control neural signals that modulate mood and behaviour along and have a vital role in the aetiology of major depression (MDD), schizophrenia (SHZ) and bipolar disorder (BD). Genome-wide association studies (GWAS) have reported several dopaminergic pathway’s and other genetic loci’s association with these disorders, therefore, the present study was conducted to analyse the GWAS and candidate gene loci of the dopaminergic and cognitive system genes in MDD, SHZ, and BD, in the Pakistani population. A total of 1237 subjects [MDD n = 479; BD n = 222; SHZ n = 146; and controls n = 390], were screened for eleven genetic variants through polymerase chain reaction (PCR) techniques. Univariant followed by multivariant logistic regression analysis were applied to determine the genetic association. Significant risk associations were observed for rs4532 and rs1799732 with MDD; and rs1006737 and rs2238056 with BD. However, after applying multiple test corrections rs4532 and rs1799732 association did not remain significant for MDD. Moreover, a protective association was found for three variants DRD4-120bp, rs10033951 and rs2388334 in the current cohort. Thus, in conclusion, the current study revealed the risk association of rs1006737 and rs2238056 with BD and the protective effect of DRD4-120bp in MDD and BD, of rs2388334 in BD and of rs10033951 in MDD, BD, and SHZ in the current Pakistani cohort.