In a genome-wide association study published in JAMA Psychiatry, the semaphorin 3A (SEMA3A) locus was associated with alcohol dependence and major depressive disorder in African American individuals.

Researchers evaluated genome-wide association data from independent samples of African American (n=4653) and European American participants (n=3169) from 2 Yale-Penn study samples, which were analyzed independently as well. They evaluated the association between the findings, polygenic risk scores, and comorbid alcohol dependence and major depressive disorder for each sample. Comorbid alcohol dependence and depression were each measured using comorbid criterion counts ranging from 0 to 14 as defined by the DSM-IV.

Among African American participants, the SEMA3A locus was associated with comorbid alcohol dependence and major depression in both Yale-Penn sample 1 (β = 0.89; 95% CI, 0.57-1.20; P <.001) and Yale-Penn sample 2 (β = 0.83; 95% CI, 0.39-1.28; P <.001). When the samples were combined, the study authors reported a more robust association (β = 0.87; 95% CI, 0.61-1.12; P <.001), but no such association was noted among the European American populations.

Higher risk of alcohol dependence and major depression comorbidity was associated with a higher polygenic risk score for neuroticism (β = 1.01; 95% CI, 0.50-1.52), a higher risk score for depressive symptoms (β = 0.87; 95% CI, 0.32-1.42), a lower risk score for subjective well-being (β = -0.94; 95% CI, -1.46 to -0.42), and a lower risk score for educational attainment (β = -1.00, 95% CI, -1.57 to -0.44).

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Furthermore, polygenic risk scores for larger intracranial (β = 1.07; 95% CI, 0.50 to 1.64) and smaller putamen volumes (β = -1.16; 95% CI, -1.86 to -0.46) were associated with increased risk of comorbid alcohol dependence and depression.

The study authors stated their results “support the conclusion that these comorbid traits [of alcohol dependence and depression] 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.”


Zhou H, Polimanti R, Yang B-Z, et al. Genetic risk variants associated with comorbid alcohol dependence and major depression [published online October 25, 2017]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2017.3275