The genetics of complex human behaviour: Cannabis use, personality, sexuality and mating

Abstract

I investigated the genetic and environmental etiology of individual differences in a variety of complex human behaviours, broadly captured within three domains - 1) cannabis use, 2) personality, and 3) sexuality and mating. Research questions and hypotheses are addressed with large community-based, genetically informative datasets and various methodological and statistical approaches. Section I focuses on the genetics of cannabis use. By meta-analysing existing twin studies I determined more precisely the relative contributions of genes and environment on individual differences in cannabis use and abuse. For cannabis use initiation I found a heritability estimate of 48% in males and 40% in females. For problematic cannabis use the heritability estimates were 51% and 59% for males and females. I then performed a gene-based association test on a large sample to test for genetic association between ten previously reported candidate genes and lifetime frequency of cannabis use. None of the candidate genes reached even nominal significance, which may point to our limited understanding of the neurobiology of cannabis use and also to potential publication bias and false-positive findings in previous studies. To identify potential new genetic variants underlying cannabis use, I then meta-analysed results from two large genome-wide association studies for cannabis use initiation. I did not identify any genetic variant significantly contributing to cannabis use initiation. Furthermore, I estimated that only approximately 6% of variance in cannabis initiation is due to common genetic variants. This suggests that non-additive effects, and/or rare mutations may also play a role in cannabis use vulnerability. Section II focuses on personality traits, which are known to be moderately heritable. I performed the first genome-wide association study on Cloninger’s personality traits to identify genetic variants underlying personality, followed by a meta-analysis of four genome-wide association studies. I also performed gene-based association tests and investigated if genes in specific biological pathways showed elevated association with personality traits. Additionally, I performed a genetic prediction analysis to test if the aggregated effects of common variants obtained from genome-wide association results from a discovery sample could predict personality in another sample. In both studies no genetic variants or pathways were found to be significantly related to any personality trait, nor could the genetic prediction scores explain a substantial part of the variation in any personality dimension. Our findings indicate that individual common genetic variants with an effect size of more than ~0.5% do not contribute to personality variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained. In the next study, I tested these different evolutionary mechanisms by estimating the percentage of the genetic variation underlying personality attributable to the combined effect of common variants by using a newly developed methodology utilising genome-wide single nucleotide polymorphism data; I also investigated whether inbreeding affects personality. I estimated that little variation in the personality traits is due to the combined effect of common, additive genetic variants, suggesting that most heritable variation in personality is due to rare variant effects and/or some combination of dominance and epistasis. Furthermore, higher levels of inbreeding were associated with less socially-desirable personality trait levels in three of the four personality dimensions. These findings are consistent with genetic variation in personality traits having been maintained by mutation-selection balance. Section III focuses on human sexuality and mating. By employing the classical twin design, I found that individual differences in risky sexual behaviour are influenced to the same extent by genes, shared environment and residual influences. Moreover, risky sexual behaviour is associated with adolescent misconduct in other domains, primarily because of genetic correlation between the variables. I then investigated the etiology of elevated lifetime depression rates in homosexuals and bisexuals as compared to heterosexuals in a genetically informative sample. Analyses revealed that genetic factors account for the majority of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were also significant predictors of both sexual orientation and depression, further contributing to their correlation. The last three studies investigated the genetic and environmental influences on human mate preferences and realised choices on a wide variety of physical and behavioural traits. Mate preferences showed substantial heritability, whereas for realised mate-choice the average heritability was near-zero. I also found that mate choice is not significantly influenced by sexual imprinting, where individuals acquire mate-choice criteria by using their opposite-sex parent as the template of a desirable mate. The main detectable pattern of mate choice was assortative mating, which I showed is likely due to both phenotypic matching (choosing a partner based on their self-similarity) and social homogamy (choosing a partner from within one’s social group, which includes individuals who tend to be self-similar). Following the empirical papers, I provide a general discussion in which I summarise the findings and their implications, mention potential limitations of the research, and suggest directions for future research.