Behavioural

Major Depression and Alcohol Dependence (Comorbid)

Reviewed September 11, 2026

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.

What this condition connects to

Major Depression and Alcohol Dependence (Comorbid) Variant: rs139438618 rs139438618 Variant Variant: rs2066702 rs2066702 Variant Major Depression and Alcohol Dependence (Comorbid) Major Depression and Alcohol Behavioural
Prevalence
Zhou et al. 2017 analysed 7,822 Yale-Penn study participants (4,653 African American, 3,169 European American, analysed separately) for combined DSM-IV criterion counts of alcohol dependence and major depression. A SEMA3A-region variant reached significance and replicated in African American participants (meta-analysis P = 2.4x10^-11); no significant association was found in European American participants (PMID:29071344).
Inheritance
A common variant significant and replicated in African American participants specifically, with no significant association found in European American participants analysed in the same study — an ancestry-specific finding, not a universal one.

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.

One variant, found only in African American participants

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.

Clinical detail

What is actually diagnosed and treated here

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.

Related here

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.

Related variants MyGeneLog™ checks for

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.

Sensitive

Major depression and alcohol dependence

SEMA3A · rs139438618

See detailed info →
Standard

Alcohol dependence

ADH1B · rs2066702

See detailed info →

Sources

Databases, guidelines and references

Papers, with their authors

Questions about Major Depression and Alcohol Dependence (Comorbid)

Can this variant diagnose depression, alcohol dependence, or both together?

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.

Is this the same as the Depression page or the Major Depressive Disorder page already on this site?

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.

Does this variant matter for people who are not African American?

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.

What does SEMA3A do?

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.

Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.