Common genetic contributions to alcohol and cannabis use and dependence symptomatology

Abstract

Background: Despite mounting evidence that use of and dependence on alcohol and cannabis are influenced by heritable factors, the extent to which heritable influences on these phenotypes overlap across the 2 substances has only rarely been explored. In the current study, we quantified cross-substance overlap in sources of variance and estimated the degree to which within-substance associations between use and dependence measures are attributable to common genetic and environmental factors for alcohol and cannabis.

Methods: The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 735 singletons) from the Australian Twin Registry, aged 24 to 36 years. Alcohol and cannabis use histories were collected via telephone diagnostic interviews and used to derive an alcohol consumption factor, a frequency measure for cannabis use, and DSM-IV alcohol and cannabis dependence symptom counts. Standard genetic analyses were conducted to produce a quadrivariate model that provided estimates of overlap in genetic and environmental influences across the 4 phenotypes.

Results: Over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms, and just under 50% of variance in alcohol dependence (AD) symptoms were attributable to genetic sources. Shared environmental factors did not contribute significantly to the 4 phenotypes. Nearly complete overlap in heritable influences was observed for within-substance measures of use and dependence symptoms. Genetic correlations across substances were 0.68 and 0.62 for use and dependence symptoms, respectively.

Conclusions: Common heritable influences were evident for alcohol and cannabis use and for AD and cannabis dependence symptomatology, but findings indicate that substance-specific influences account for the majority of the genetic variance in the cannabis use and dependence phenotypes. By contrast, the substantial correlations between alcohol use and AD symptoms and between cannabis use and cannabis dependence symptoms suggest that measures of heaviness of use capture much of the same genetic liability to alcohol- and cannabis-related problems as dependence symptomatology.

Figure 1. Rates (%) of Alcohol Dependence Across Varying Levels of Alcohol Consumption By Sex

Figure 2. Rates (%) of Cannabis Dependence Across Varying Levels of Cannabis Use By Sex

Figure 3. Unstandardized Additive Genetic Path Estimates For the Four Phenotypes

Raw path estimates are shown in Figure 3. Calculation of genetic variance from common and specific sources is illustrated below for cannabis dependence symptoms: Total genetic variance = (.6182)² + (.1928)² + (.5021)² = 0.6715 Variance explained by A1 (genetic influences common to all four phenotypes) = (.5021)²/.6715 = .3754* Variance explained by A2 (genetic influences shared by alcohol consumption, cannabis dependence symptoms, and cannabis use) = (.1928)²/.6715 = .0554** Variance explained by A3 (genetic influences common to cannabis dependence symptoms and cannabis use) = (.6182)²/.6715 = .5691 *From Table 6, the genetic correlation between alcohol dependence symptoms and cannabis dependence symptoms is 0.6128, which is computed as √.3754 **From Table 6, the genetic correlation between alcohol consumption and cannabis dependence symptoms is 0.6558. This is NOT equal to √.0554. To calculate this correlation, we compute the total genetic covariance across the two measures, including variance shared with alcohol dependence symptoms, and divide it by the product of the square root of the total genetic variance in alcohol consumption and cannabis dependence symptoms. Therefore, 0.6558 = (.2362 × .1928) + (.7445 × .5021) / [(√0.6715) × (√0.6100)] where .6100 = (.2362)² + (.7445)² = the total genetic variance in alcohol consumption explained by A1 and A2.