A genetic predisposition to alcohol use is not the same as a genetic destiny for alcohol misuse

There is a clear relationship between alcohol and neurodegeneration; for example, an alcohol use disorder correlates with a higher risk of Alzheimer’s disease. It is unclear, however, whether individual differences in brain structure and connectivity are risk factors for, or consequences of, alcohol use. New research exploring this relationship will be shared on Wednesday, 26 June 2024 at the 47^th annual scientific meeting of the Research Society on Alcohol (RSA) in Minneapolis, Minnesota.

“Although we have known for a long time that alcohol consumption is linked to individual differences in the brain,” explained Jeanne Savage, a research associate at Vrije Universiteit Amsterdam, “it is extremely difficult to tease apart whether these are solely caused by alcohol exposure or whether an underlying genetic vulnerability shapes one’s likelihood of both alcohol use and neurodegeneration.”

Neurodegeneration is itself a consequence of chronic heavy alcohol use. “There are a number of neurodegenerative disorders, such as alcohol-induced dementias, that are directly caused by alcohol,” said Savage. “The role of alcohol on neural functioning can also be clearly seen from the damaging effects of in utero exposure on early neurodevelopment. Alcohol and its by-products are toxic, and when consumed in large amounts, they can trigger an inflammatory response that can damage cells – especially brain cells – or prevent new cells from developing.”

At the same time, genetic influences are important for alcohol use behaviors – accounting for about 50 percent of a person’s predisposition to alcohol use disorders.

For this study, researchers examined whether three sets of previously examined genes were linked to a variety of brain measures. Using data from a very large British database of older adults who have completed multiple surveys, provided medical records, and participated in MRI scans to create 3D images of their brains, the researchers were able to map genetic influences on the volume of brain regions that have previously been linked to alcohol use behaviors.

Initial results showed that genetic predispositions for alcohol consumption and alcohol problems were associated with different brain volumes. “Genes linked to alcohol ‘problems’ were associated with smaller overall brain volume and smaller volume of the striatum, an integral part of the reward system,” explained Savage. “Genes linked to alcohol ‘consumption’ showed an opposite pattern. These findings suggest that brain differences may help explain why some individuals are able to drink alcohol in high quantities without experiencing problems. In other words, we showed that genetic influences on alcohol use behaviors are indeed linked to structural brain differences, but they are neither uniform nor deterministic.”

Savage plans to continue her work to understand how genetic predispositions have their effect in order to understand the underlying biology. “Equally important,” she said, “is for individuals who carry these predispositions to know that genes are not destiny.”