Genetic Factors Shared Between MDD, Alcohol Dependence

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The association between MDD polygenic risk score and alcohol dependence remained significant after adjustment for MDD status in three of the data sets.
The association between MDD polygenic risk score and alcohol dependence remained significant after adjustment for MDD status in three of the data sets.

Major depressive disorder (MDD) and alcohol dependence (AD) share common genetic factors, according to a recent large-scale association analysis published in JAMA Psychiatry.

Researchers conducted association analyses of MDD polygenic risk scores and alcohol dependence using data from 4 independent genome-wide association studies (GWAS). Participants were from the Collaborative Study on the Genetics of Alcoholism (COGA; n=788 cases, 522 controls); the Study of Addiction, Genetics, and Environment (SAGE; n=631 cases, 350 controls); the Yale-Penn genetic study of substance dependence (n=2135 cases, 350 controls); and the National Health and Resilience in Veterans Study (NHRVS; n=317 cases, 1719 controls). MDD polygenic risk scores were calculated from the Psychiatric Genomics Consortium meta-analysis of MDD and AD case-control status.

In all 4 data sets, higher MDD polygenic risk score was associated with a significant increase in the risk of alcohol dependence (COGA: P <.001; SAGE: P =.001; Yale-Penn:

P =.04; NHRVS: P =.004). When the samples were combined in a meta-analysis, researchers indicated that the association between MDD and PRS was even stronger (P <.001).

The association between MDD polygenic risk score and alcohol dependence remained significant after adjustment for MDD status in three of the data sets (COGA: P <.001; Yale-Penn P =.08; NHRVS: P =.006).

When the MDD polygenic risk score was recalculated using MDD GWAS data sets without comorbid MDD-alcohol dependence cases, a significant association between MDD and alcohol dependence remained (P =.007).

Shizhong Han, PhD, corresponding investigator in the study, said, "This is the first time that we provided consistent evidence of [shared risk factors for alcohol dependence and depression] at a molecular genetic level." Future studies will need to evaluate "the particular genes or biological pathways underlying both disorders," which are still unknown.

References

Andersen AM, Pietrzak RH, Kranzler HR. Polygenic scores for major depressive disorder and risk of alcohol dependence [published online August 16, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.2269



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