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

Ingeborg Bolstad,Jenny Skumsnes Moe,Jørg Gustav Mørland,Jørgen Gustav Bramness

doi:10.1016/j.psychres.2021.114257

Abstract

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.

Highlights

Genetic vulnerability for alcohol use disorders (AUD) and depressive disorders (DD) continues to be widely investigated
We explored the relationship between 26 candidate gene single nucleotide polymorphisms (SNPs), alcohol consumption and mental distress in a multipurpose case-control sample (n = 1978, 49% women) derived from a Norwegian general population sample
When comparing background variables to Cohort of Norway (CONOR) Mental Health Index. SD (CMHI-5), mental distress was higher in unmarried participants (p < 0.05 women, p < 0.0001 men), and for women if they were smoking currently (p < 0.05) or had a somatic disease (p

Summary

Introduction

Genetic vulnerability for alcohol use disorders (AUD) and depressive disorders (DD) continues to be widely investigated. Recent epidemiological studies suggest a positive correlation between alcohol consumption and depressive symptoms (Gigantesco et al, 2015; Jokela et al, 2020; Mathiesen et al, 2012) which is in turn associated with increased morbidity and mortality (Degerud et al, 2020), high lighting the need for further investigations. The prevalence and presentation of both alcohol consumption and depressive symptoms are strongly influenced by gender (WHO, 2013). A recent follow-up study on depression GWAS found the majority of gene prod ucts to have a sex specific expression (Wu et al, 2021). This supports an earlier study which found that genes contribute to depression risk in a sex specific manner (Zhao et al, 2020)

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