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Research shows that the polygenic score calculated using concordant single-nucleotide variants may be a method to evaluate risk for alcohol use disorder.

The polygenic score (PGS) calculated using concordant single-nucleotide variants may be a method to evaluate risk for alcohol use disorder (AUD), as shown by findings from a genetic association study published in JAMA Network Open.

For the study, Dongbing Lai, PhD, and colleagues assessed the estimability and generalizability of the PGS, which measures an individual’s genetic liability, in comparison with family history and ADH1B in evaluating the risk for AUD among populations of European ancestry.

The researchers used the pruning and thresholding method in a 2-stage design to calculate PGSs in the screening stage. Then, they determined the estimability and generalizability of the best PGS using 2 independent samples in the testing stage. Because accurate diagnosis of cases and controls is critical for screening PGS, the authors used 3 datasets from cohorts ascertained to study AUD: the Collaborative Study on the Genetics of Alcoholism, the Study of Addiction: Genetics and Environment, and the Australian Twin-Family Study of Alcohol Use Disorder. The All of Us Research Program (AOU), which comprises patients with diverse backgrounds and conditions, and the Indiana Biobank (IB), consisting of Indiana University Health System patients, were used to test the best PGS.

The 3 cohorts included a total of 8,799 samples (6,323 cases and 2,476 controls; 50.6% were men and 49.4% were women). The AOU cohort had a total of 116,064 samples (5,660 cases and 110,404 controls; 39.6% were men and 60.4% were women). The IB cohort included 6,373 samples (936 cases and 5,437 controls; 45.1% were men and 54.9% were women).

The top 5% of samples had the highest risk in both the AOU (odds ratio [OR], 1.96; 95% CI, 1.78-2.16) and IB (OR, 2.07; 95% CI, 1.59-2.71) cohorts, and they were 2 times more likely to develop AUD compared with the remaining 95% of samples; these ORs were comparable to family history of AUD. For the bottom 5% of samples with the lowest PGS in the AOU and IB cohorts, the risk for AUD was approximately half (OR, 0.53; 95% CI, 0.45-0.62 and OR, 0.57; 95% CI, 0.39-0.84, respectively); these ORs were comparable to the protective effect of ADH1B. Overall, PGS had similar results for both men and women, according to the study results.

“Future studies will aim to further improve the generalizability of PGS by testing datasets with similar AUD prevalence as in general populations,” noted the researchers. “Additionally, we will develop a PGS that can be used to estimate AUD risk in populations of non-European ancestry.”