What is the Genetic Basis for Alcohol Dependence and Major Depression?

major depression

A recent study sheds new light on the genetic basis of alcohol dependence and major depression, which could help develop new treatments for these conditions.

Although the comorbidity of alcohol dependence and major depression is recognized, the underlying basis of their co-occurrence is not well understood. Studies indicate that alcohol dependence increases the risk of major depression1 and conversely, major depression increases the risk of alcohol dependence.2 A new genome-wide association study attempted to understand the underlying genetic basis of the association between the two conditions, and its results were published recently in JAMA Psychiatry.3 The study recruited a total of 7,822 participants who were divided into two groups, and their data were analyzed separately. The first group comprised of 4,653 African American participants, and the second group comprised of 3,169 European American participants. The researchers interviewed the participants to derive information about their alcohol dependence and major depression status. The participants were then genotyped and the single nucleotide variants examined for the association.

The study found a significant association between the single nucleotide variant rs139438618 and both alcohol dependence and major depression in the African American group. The association of this single nucleotide variant with comorbidity was not significant for the European American group.

The study also noted that individuals who had higher polygenic risk scores (a score that captures the risk of having a particular trait based on the weighted contributions from multiple genetic loci) for neuroticism and depression were more likely to be comorbid for alcohol dependence and major depression. On the other hand, the polygenic risk scores for feelings of overall well-being and educational attainment were negatively associated with the comorbidity risk. Furthermore, the polygenic risk scores for intracranial volume was positively associated with comorbidity for alcohol dependence and major depression, whereas the polygenic risk score for putamen volume was negatively associated with the comorbidity for these conditions.

The rs139438618 single nucleotide polymorphism is located in an intron of the SEMA3A gene, which codes for the semaphorin-3A protein that is essential for the development of normal neuronal patterns. However, the underlying molecular basis of the association between this locus and comorbidity of alcohol dependence and major depression is not known and will require further studies. The association of this single nucleotide polymorphism with comorbidity only in the African American group indicates a population-specific genetic risk.

The authors conclude by noting that these two comorbid conditions may be considered a single genetic trait that is influenced by a single or few genetic variants and express the need for further studies to delineate the underlying molecular mechanisms involved.

Written by Usha B. Nair, Ph.D.

References

1) Fergusson DM, Boden JM, Horwood LJ. Tests of causal links between alcohol abuse or dependence and major depression. Arch Gen Psychiatry. 2009 Mar;66(3):260-6. doi:10.1001/archgenpsychiatry.2008.543. PubMed PMID: 19255375.
2) Kuo PH, Gardner CO, Kendler KS, Prescott CA. The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design. Psychol Med. 2006 Aug;36(8):1153-62. Epub 2006 May 31. PubMed PMID: 16734951.
3) Zhou H, Polimanti R, Yang BZ, Wang Q, Han S, Sherva R, Nuñez YZ, Zhao H, Farrer LA, Kranzler HR, Gelernter J. Genetic risk variants associated with comorbid alcohol dependence and major depression. JAMA Psychiatry. 2017 Oct 25.doi: 10.1001/jamapsychiatry.2017.3275. [Epub ahead of print] PubMed PMID: 29071344.