24Alcohol use is correlated within spouse-pairs, but it is difficult to disentangle 25 the effects of alcohol consumption on mate-selection from social factors or 26 cohabitation leading to spouses becoming more similar over time. We hypothesised 27 that genetic variants related to alcohol consumption may, via their effect on alcohol 28 behaviour, influence mate selection. 29Therefore, in a sample of over 47,000 spouse-pairs in the UK Biobank we 30 utilised a well-characterised alcohol related variant, rs1229984 in ADH1B, as a 31 genetic proxy for alcohol use. We compared the phenotypic concordance between 32 spouses for self-reported alcohol use with the association between an individual's 33 self-reported alcohol use and their partner's rs1229984 genotype using Mendelian 34 randomization. This was followed up by an exploration of the spousal genotypic 35 concordance for the variant and an analysis determining if relationship length may be 36 related to spousal alcohol behaviour similarities. 37We found strong evidence that both an individual's self-reported alcohol 38 consumption and rs1229984 genotype are associated with their partner's self-39 reported alcohol use. The Mendelian randomization analysis found that each unit 40 increase in an individual's weekly alcohol consumption increased their partner's 41 alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P=1.10x10 -5 ). Furthermore, 42 the rs1229984 genotype was concordant within spouse-pairs, suggesting that some 43 spousal concordance for alcohol consumption existed prior to cohabitation. Although 44 the SNP is strongly associated with ancestry, our results suggest that this 45 concordance is unlikely to be explained by population stratification. Overall, our 46 findings suggest that alcohol behaviour directly influences mate selection. 47 their partner's rs1229984 genotype, a missense mutation in ADH1B strongly 97 associated with alcohol consumption as an instrumental variable for self-reported 98 alcohol consumption. Third, we estimated the association of rs1229984 genotype 99 between spouses, to evaluate the timing of possible causal effects, and investigate 100 the possibility of bias from population stratification. Fourth, using the mean age of 101 each couple as a proxy for relationship duration, we determined if there was an 102 association between longer relationships and more similar spousal alcohol 103 behaviour. As a positive control, to demonstrate the validity of derived spouse pairs 104 and the usage of a Mendelian randomization framework, we also analysed height, 105 known to be correlated between spouses, using similar methods. 106
Materials and Methods107 Study participants 108 UK Biobank 109 UK Biobank is a large-scale cohort study, including 502,655 participants aged 110 between 40-69 years. Study participants were recruited from 22 recruitment centres 111 across the United Kingdom between 2006 and 2010 36 37 . For the purposes of our 112 analyses, we restricted the dataset to a subset of 463,827 individuals of recent 113 European...
