Newswise — A new study has shown that alcohol-related diseases are driven by both environmental and genetic factors, a proportion of which are not shared with the underlying alcohol use disorder (AUD). Medical conditions resulting from alcohol misuse include alcoholic liver disease, pancreatitis, cardiomyopathy, and neuropathy − but not everyone with AUD experiences medical issues linked to their drinking. The factors that influence liability to alcohol-related medical conditions (AMCs) in people with AUD are not fully understood. In a large study reported in Alcoholism: Clinical and Experimental Research, researchers from Sweden and the United States quantified the extent to which genetic and environmental factors shared with, versus distinct from, AUD contribute to progression to AMC.

The researchers used Swedish medical and criminal registries to identify pairs of identical and non-identical twins, full siblings, and half-siblings where at least one of the pair had documented AUD. Next, they identified which of these individuals had also been diagnosed with one (or more) of ten AMCs. By studying the correlation of AUD and AMC among sibling-pairs of differing genetic relatedness, and fitting statistical models to the data, the researchers were able to tease out the genetic and environmental sources of variance that contribute to AUC and AMC liability.

Overall, 3% of women and 9% of men in the analzyed birth cohort had AUD (totaling ~86,000 people), and of these 14% of women and 15% of men had an AMC (~13,000 people). The proportion of sibling-pairs in which both siblings had AUD, or in which both siblings had an AMC, generally decreased as genetic relatedness decreased; this suggests a role of genetic factors in both AUD and AMC. Overall, around one third of the risk for AMC was found to be genetic, while two-thirds of the risk could be attributed to environmental factors. Of note, most (77%) of the environmental influence on AMC was unique to AMC (rather than shared with that for AUD), as was around 40% of the genetic influence.

The findings confirm the relevance of AMC-specific genetic factors, highlighting a need for additional studies to identify the genes involved and determine how they contribute to AMC etiology − potentially through metabolic pathways or physiological responses to toxins or damage. The findings also highlight the considerable influence of AMC-specific environmental factors, offering an important opportunity for follow-up studies to identify exposures that distinguish individuals with AUD who do versus do not develop AMC. Relevant environmental factors, some of which may be modifiable and therefore viable targets for prevention, might include other medical conditions, lack of preventative care, and diet. Additionally, the finding that some genetic and environmental liability for AMC is shared with AUD underscores that ongoing efforts to prevent AUD will have an overall positive impact, reducing the personal and economic toll of AMC as well as of AUD.

The researchers note some limitations. First, the analyses collapsed a wide range of different AMCs into a single AMC outcome, potentially obscuring important etiologic differences across different body organs impacted by heavy alcohol use. Second, the risk of AMC is likely to be at least partly dependent on the level of alcohol consumption, for which data were not available. These factors should be explored in future studies. It is also unclear whether the findings can be generalized to countries without socialized medicine, such as the US. For example, reduced access to AUD treatment among some patient groups, such as the socioeconomically disadvantaged, might impact AUD/AMC associations.

Genetic and environmental influences on the progression from alcohol use disorder to alcohol-related medical conditions. Alexis C. Edwards, K. Sundquist, J. Sundquist, K. S. Kendler, S. Larsson Lönn (pages xxx).

ACER-21-4978.R1

SEE ORIGINAL STUDY