GABAA subunit single nucleotide polymorphisms show sex-specific association to alcohol consumption and mental distress in a Norwegian population-based sample

Little is known about genetic influences on the relationship between alcohol consumption and mental distress in the general population, where the majority report consumption and distress far below diagnostic thresholds. This study investigated single nucleotide polymorphisms (SNPs) from candidate gene studies on alcohol use disorder and depressive disorders, for association with alcohol consumption and with mental distress in a population-based sample from the Cohort of Norway (n = 1978, 49% women). The relationship between alcohol consumption and mental distress was further examined for genotype modification. There was a positive correlation between mental distress and alcohol consumption in men, as well as an association between SNPs and mental distress in men (GABRG1, GABRA2, DRD2, ANKK1, MTHFR) and women (CHRM2, MTHFR) and between SNPs and alcohol consumption in women (GABRA2, MTHFR). No modification by SNP genotype was found on the relationship between alcohol consumption and mental distress. The association between mental distress and GABRG1 in men remained significant after correcting for multiple comparisons. The results indicate that alcohol consumption and mental distress are associated in the general population even at levels below clinical thresholds and point to SNPs in genes related to GABAergic signalling for level of mental distress in men.