The genetic architecture of substance use

The use of substances such as alcohol, tobacco, cannabis, and cocaine, places an enormous burden on substance users themselves, their families, and society. Although current psychological and pharmacological treatments for substance use disorders have demonstrated positive treatment outcomes, the effects are moderate at best and many patients do not benefit from these treatments. To improve treatment and prevention strategies it is crucial to gain a better understanding of the psychological and biological mechanisms underlying substance use disorders.
Twin studies have shown heritability estimates of 40-85% for substance use disorders, indicating that a substantial proportion of the susceptibility to substance use is determined by our genetic profile.
This thesis examined, therefore, the role of genetic variants in the susceptibility to substance use. Furthermore, we examined the genetic overlap between substance use traits, psychiatric disorders and socioeconomic status (SES). We found that rare genetic variants do not play a large role in alcohol consumption and tobacco use. However, our analyses revealed significant association between common genetic variants and these traits. Furthermore, using a method incorporating functional information, we found 23 novel candidate variants for substance use traits, and identified candidate genes and tissues through which these candidate loci potentially exert their effect. Using methods to estimate the genetic overlap between traits, we found evidence that the genetic overlap between substance use traits and psychiatric disorders might be mediated through SES. Moreover, we found that the phenotypic heterogeneity of major depressive disorder also exist on a genetic level.