Genetic and shared couple environmental contributions to smoking and alcohol use in the UK population

Abstract

Alcohol use and smoking are leading causes of death and disability worldwide. Both genetic and environmental factors have been shown to influence individual differences in the use of these substances. In the present study we tested whether genetic factors, modelled alongside common family environment, explained phenotypic variance in alcohol use and smoking behaviour in the Generation Scotland (GS) family sample of up to 19,377 individuals. SNP and pedigree-associated effects combined explained between 18 and 41% of the variance in substance use. Shared couple effects explained a significant amount of variance across all substance use traits, particularly alcohol intake, for which 38% of the phenotypic variance was explained. We tested whether the within-couple substance use associations were due to assortative mating by testing the association between partner polygenic risk scores in 34,987 couple pairs from the UK Biobank (UKB). No significant association between partner polygenic risk scores were observed. Associations between an individual's alcohol PRS (b = 0.05, S.E. = 0.006, p < 2 × 10 −16) and smoking status PRS (b = 0.05, S.E. = 0.005, p < 2 × 10 −16) were found with their partner's phenotype. In support of this, G carriers of a functional ADH1B polymorphism (rs1229984), known to be associated with greater alcohol intake, were found to consume less alcohol if they had a partner who carried an A allele at this SNP. Together these results show that the shared couple environment contributes significantly to patterns of substance use. It is unclear whether this is due to shared environmental factors, assortative mating, or indirect genetic effects. Future studies would benefit from longitudinal data and larger sample sizes to assess this further.

Dissecting indirect genetic effects from peers in laboratory mice

“…The analysis of the genetic correlation ρ between DGE and IGE for the same phenotype provides insights into the overlap between DGE and IGE loci for a given phenotype and whether the traits mediating IGE on a phenotype of interest are genetically correlated (in the classical sense) with that phenotype. The correlation ρ was expected to be different from zero for many phenotypes, based on reports that emotions(52–54), behaviours(25, 55, 56), pathogens, and components of the gut microbiome(57) can “spread” between individuals and contribute to phenotypic variation, both in mice and in humans. In our study we found that ρ is significantly different from zero for a variety of phenotypes, which indicates some overlap between DGE loci and IGE loci for the same trait and is consistent with a genetic correlation (in the classical sense) between the phenotype of interest and the traits mediating IGE.…”

Disentangling Social-Genetic From Rearing-Environment Effects for Alcohol Use Disorder Using Swedish National Data

“…In human samples, findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health) indicated that friends’ and schoolmates’ genotypes predicted educational attainment (Domingue et al, 2018) and smoking behavior (Sotoudeh, Harris, & Conley, 2019). In the UK BioBank sample, individuals whose spouses carried the protective A allele of the ADH1B single-nucleotide polymorphism rs1229984 drank less compared with those whose spouses were not carriers (Clarke et al, 2019).…”

Genetic assortative mating for schizophrenia and bipolar disorder

“…Accordingly, a positive correlation between partners’ PRS for a trait would provide evidence for trait-specific genetic assortative mating with consequences for population-level genetics. Trait-specific genetic assortative mating has previously been demonstrated for educational attainment, height, body mass index, smoking, and alcohol consumption [ 11 – 13 , 15 , 18 – 21 ], but it is not commonly investigated in the context of psychiatric disorders. Yengo et al [ 13 ] investigated genetic assortative mating for 32 complex traits and found statistically significant correlations between partners’ PRSs for height and educational attainment, but not for any psychiatric disorder, after correction for multiple comparisons.…”