Study identifies genetic variant linked to comorbid alcohol addiction, depression

Recent findings indicated a genetic variant associated with comorbid alcohol dependence and major depression in black Americans.

“Genome-wide association studies have reported genome-wide significant findings for [alcohol dependence] and [major depression],” Hang Zhou, PhD, of Yale University School of Medicine, and colleagues wrote. “However, thus far, no findings have been reported for comorbid [alcohol dependence] and [major depression].”

To determine genetic risk variants for comorbid alcohol dependence and major depression, researchers analyzed criterion counts of comorbid alcohol dependence and major depression in black and white American data sets in the Yale-Penn study of genetics of drug and alcohol dependence. Analysis included 4,653 black individuals and 3,169 white individuals. Median comorbid criterion count was 6.2.

A linear regression model indicated a significant association between rs139438618 at the semaphorin 3A (SEMA3A [OMIM 603961]) locus and alcohol dependence and major depression comorbidity in black participants in the Yale-Penn 1 sample ( = 0.89; 95% CI, 0.57-1.2).

The association was also significant in the independent Yale-Penn 2 sample, ( = 0.83; 95% CI, 0.39-1.28).

Meta-analysis of the two samples indicated a more robust association ( = 0.87; 95% CI, 0.61-1.12). There was no significant association among white participants.

Analyses of polygenic risk scores showed that individuals with a higher risk for neuroticism ( = 1.01; 95% CI, 0.5-1.52) or depressive symptoms ( = 0.87; 95% CI, 0.32-1.42) and a lower level of subjective well-being ( = –0.94; 95% CI, –1.46 to –0.42) and educational attainment ( = –1, 95% CI, 1.57 to –0.44) had higher levels of alcohol dependence and major depression comorbidity.

Larger intracranial ( = 1.07; 95% CI, 0.5-1.64) and smaller putamen volumes ( = –1.16; 95% CI, –1.86 to –0.46) were associated with higher risks for alcohol dependence and major depression comorbidity.

“Our findings thus support the conclusion that these comorbid traits may be to some extent, and may be considered for some purposes, a single diagnostic, or even genetic, entity: that is, among individuals with comorbid [alcohol dependence] and [major depression], there are some in whom the risk for both illnesses is influenced by a single, or a few, variants,” the researchers wrote. “Further efforts to elucidate the molecular risk factors and the causal mechanisms for comorbid [alcohol dependence] and [major depression] will require larger samples to enable a focus on lower-frequency and rare variants that may have large effects.” – by Amanda Oldt

Disclosures: Zhou reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.