Seeking a Genetic Link Between Depression and Alcohol Dependence

People with an elevated polygenic risk for major depressive disorder (MDD) may also be at risk for alcohol dependence (AD), according to a study in JAMA Psychiatry.

The researchers found that a shared genetic susceptibility has a modest contribution to the comorbidity of MDD and AD.

The study analyzed data from participants in a variety of other studies: 788 cases and 522 controls from the Collaborative Study on the Genetics of Alcoholism (COGA); 631 cases and 756 controls from the Study of Addiction, Genetics, and Environment (SAGE); 2135 cases and 350 controls from the Yale-Penn genetic study of substance dependence (Yale-Penn); and 317 cases and 1719 controls from the National Health and Resilience in Veterans Study (NHRVS).

The risk of AD was significantly increased in all samples in people with a higher MDD polygenic risk score:(COGA: best P =1.7 x 10⁻⁶, R² =.026; SAGE: best P =.001, R² =.01; Yale-Penn: best P =.035, R² =.0018; and NHRVS: best P =.004, R² =.0074). There was stronger evidence for an association after meta-analysis of all 4 samples (best P =3.3 x 10⁻⁹).

The researchers interpret the findings as suggesting that shared genetic factors may be partly responsible for the bidirectional relatedness of MDD and AD.

Disclosure

Dr Kranzler has been a paid consultant, advisory board member, or continuing medical education speaker for Indivior and Lundbeck. He is also a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which was supported in the past 3 years by AbbVie, Alkermes, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, Pfizer, and XenoPort. No other conflicts were reported.

Reference

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