Depression and alcohol dependence often occur together, and this page is specifically about the genetics of that co-occurrence — a different question from either condition alone. The one variant found here was significant only in African American participants; no association reached significance in the European American participants in the same study.
Alcohol dependence and major depression are both common and frequently occur together, and genetic epidemiology has long suggested they share some of the same underlying risk. This page is about that shared risk specifically — a different, narrower question from the general-population Depression page or the Major Depressive Disorder page already on this site, neither of which is about comorbidity.
Zhou et al. 2017 analysed 7,822 participants (4,653 African American, 3,169 European American, analysed separately) from the Yale-Penn study, scoring each person on a combined count of DSM-IV alcohol dependence and major depression criteria rather than a simple case/control split.
A variant near SEMA3A (semaphorin 3A) reached significance in the African American sample (β = 0.89, P = 2.8×10⁻⁸) and replicated in an independent second African American sample from the same study (β = 0.83, P = 2.1×10⁻⁴); the meta-analysis of the two came to β = 0.87, P = 2.4×10⁻¹¹. No significant association was found in the European American participants. The paper also reports that polygenic risk scores for several related traits — higher neuroticism, more depressive symptoms, lower subjective well-being, lower educational attainment — correlated with higher comorbidity risk, alongside some brain-volume measures; those are score-level correlations across many variants, not evidence about this one variant specifically, and this page keeps the two kinds of finding separate rather than blending them.
Alcohol dependence and depression are each diagnosed clinically, using DSM criteria and a person's history — not by genotype. Treatment for co-occurring alcohol dependence and depression is typically integrated care addressing both, decided by a clinician based on the individual. Nothing on this page changes that.
This finding is ancestry-specific in a way worth stating plainly: the SEMA3A association was significant and replicated in African American participants, and not found in European American participants analysed in the same study. That is not unusual in genetics — allele frequencies and linkage patterns differ across ancestries — but it means this variant's relevance does not simply generalise to everyone.
Depression (Self-Reported Symptoms) and Major Depressive Disorder are both on this site already, and neither is about comorbidity with alcohol dependence — this page is the narrower, specific question of the two conditions occurring together.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Major Depression and Alcohol Dependence (Comorbid) comes down to these specific, well-studied positions — not a diagnosis.
Databases, guidelines and references
No. Both conditions are diagnosed clinically using DSM criteria and a person's history. This variant comes from a genome-wide association study and is not used diagnostically.
No — those pages are each about one condition on its own. This page is specifically about the genetics of alcohol dependence and depression occurring together, a narrower and different question.
Not based on this study. The SEMA3A association was significant and replicated in African American participants; no significant association was found in the European American participants analysed in the same study. This page states that rather than generalising the finding.
Semaphorin 3A. The paper identifies a statistical association with comorbid alcohol dependence and depression risk; it does not establish the biological mechanism, and this page does not invent one.
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