Human Genetic Variation Influences Alcohol’s Sedating and Stimulating

Newswise — Although estimates vary, scientists believe that 50 to 64 percent of the risk of alcohol use disorders (AUDs) is inherited. One way to identify this risk is through a person’s subjective response to alcohol. This study investigated the effects of two single-nucleotide polymorphisms (SNPs) or changes in DNA sequence called rs279858 (in the GABRA2 gene) and rs2832407 (in the GRIK1 gene) – previously linked to AUD risk – on individuals’ subjective responses to intravenously administered alcohol.

Researchers guided 93 self-identified European-American social drinkers (48 men, 45 women; 21 to 30 years of age) through three “blinded” lab sessions during which they received intravenous infusions of alcohol targeting three different blood alcohol levels of 0.00 mg%, 40 mg%, or 100 mg%. Each participant reported on their levels of stimulation or sedation on the Biphasic Alcohol Effects Scale, which were then examined against the presence of the two genetic variants.

These gene variants appeared to alter features of the alcohol dose-response relationship in specific ways. The GABRA2 rs279858*C allele enhanced stimulant responses to higher levels of alcohol, while the GRIK1 rs2832407*C allele increased sedative responses. The authors recommended further study of the effects of the two variants on alcohol-related genetic/environment interactions and behaviors, which could lead to improved treatment options.