Shared genetic etiology between alcohol dependence and major depressive disorder

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Foo, Jerome C, Streit, Fabian, Treutlein, Jens, Ripke, Stephan, Witt, Stephanie H, Strohmaier, Jana, Degenhardt, Franziska, Forstner, Andreas J, Hoffmann, Per, Soyka, Michael et al (show 21 more authors) , Dahmen, Norbert, Scherbaum, Norbert, Wodarz, Norbert, Heilmann-Heimbach, Stefanie, Herms, Stefan, Cichon, Sven, Preuss, Ulrich, Gaebel, Wolfgang, Ridinger, Monika, Hoffmann, Sabine, Schulze, Thomas G, Maier, Wolfgang, Zill, Peter, Mueller-Myhsok, Bertram ORCID: 0000-0002-0719-101X, Ising, Marcus, Lucae, Susanne, Noethen, Markus M, Mann, Karl, Kiefer, Falk, Rietschel, Marcella and Frank, Josef (2018) Shared genetic etiology between alcohol dependence and major depressive disorder. PSYCHIATRIC GENETICS, 28 (4). pp. 66-70.

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Abstract

The clinical comorbidity of alcohol dependence (AD) and major depressive disorder (MDD) is well established, whereas genetic factors influencing co-occurrence remain unclear. A recent study using polygenic risk scores (PRS) calculated based on the first-wave Psychiatric Genomics Consortium MDD meta-analysis (PGC-MDD1) suggests a modest shared genetic contribution to MDD and AD. Using a (~10 fold) larger discovery sample, we calculated PRS based on the second wave (PGC-MDD2) of results, in a severe AD case–control target sample. We found significant associations between AD disease status and MDD-PRS derived from both PGC-MDD2 (most informative P-threshold=1.0, P=0.00063, R2=0.533%) and PGC-MDD1 (P-threshold=0.2, P=0.00014, R2=0.663%) meta-analyses; the larger discovery sample did not yield additional predictive power. In contrast, calculating PRS in a MDD target sample yielded increased power when using PGC-MDD2 (P-threshold=1.0, P=0.000038, R2=1.34%) versus PGC-MDD1 (P-threshold=1.0, P=0.0013, R2=0.81%). Furthermore, when calculating PGC-MDD2 PRS in a subsample of patients with AD recruited explicitly excluding comorbid MDD, significant associations were still found (n=331; P-threshold=1.0, P=0.042, R2=0.398%). Meanwhile, in the subset of patients in which MDD was not the explicit exclusion criteria, PRS predicted more variance (n=999; P-threshold=1.0, P=0.0003, R2=0.693%). Our findings replicate the reported genetic overlap between AD and MDD and also suggest the need for improved, rigorous phenotyping to identify true shared cross-disorder genetic factors. Larger target samples are needed to reduce noise and take advantage of increasing discovery sample size.

Item Type:	Article
Uncontrolled Keywords:	alcohol dependence, disease comorbidity, genome-wide association studies, major depressive disorder, polygenic risk scores, psychiatric genomics consortium
Depositing User:	Symplectic Admin
Date Deposited:	08 Jan 2019 15:29
Last Modified:	16 Mar 2024 23:35
DOI:	10.1097/YPG.0000000000000201
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3030548