Abstract:
Background: 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
and cognitive pathway genes association with these disorders however, no such comprehensive
data was available regarding the Pakistani population.
Objective: The present study was conducted to analyse the 11 genetic variants of dopaminergic
and cognitive system genes in MDD, SHZ, and BD in the Pakistani population.
Methods: A total of 1237 subjects [MDD n = 479; BD n = 222; SHZ n = 146; and controls n = 390], were
screened for 11 genetic variants through polymerase chain reaction (PCR) techniques. Univariant
followed by multivariant logistic regression analysis was applied to determine the genetic association.
Results: 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.
Conclusions: The present study revealed the risk association of single nucleotide polymorphisms
(SNPs) rs1006737 and rs2238056 with BD and the protective effect of the DRD4-120bp variant in
MDD and BD, of rs2388334 in BD and of rs10033951 in MDD, BD, and SHZ in the current Pakistani
cohort. Thus, the study is valuable in understanding the genetic basis of MDD, BD and SHZ in the
Pakistani population, which may pave the way for future functional studies.
