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Shared genetic etiology between alcohol dependence and major depressive disorder
| Content Provider | Scilit |
|---|---|
| Author | Foo, Jerome C. Streit, Fabian Treutlein, Jens Ripke, Stephan Witt, Stephanie H. Strohmaier, Jana Degenhardt, Franziska Forstner, Andreas J. Hoffmann, Per Soyka, Michael 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 Müller-Myhsok, Bertram Ising, Marcus Lucae, Susanne Nöthen, Markus M. Mann, Karl Kiefer, Falk Rietschel, Marcella Frank, Josef |
| Copyright Year | 2018 |
| Description | Journal: Psychiatric genetics 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, R=0.533%) and PGC-MDD1 (P-threshold=0.2, P=0.00014, R=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, R=1.34%) versus PGC-MDD1 (P-threshold=1.0, P=0.0013, R=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, R=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, R=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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039372/pdf |
| Ending Page | 70 |
| Page Count | 5 |
| Starting Page | 66 |
| ISSN | 09558829 |
| e-ISSN | 14735873 |
| DOI | 10.1097/ypg.0000000000000201 |
| Journal | Psychiatric genetics |
| Issue Number | 4 |
| Volume Number | 28 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2018-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Psychiatric genetics Psychiatry and Mental Health Alcohol Dependence Disease Comorbidity Genome-wide Association Studies Major Depressive Disorder Polygenic Risk Scores Psychiatric Genomics Consortium |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Biological Psychiatry Genetics (clinical) Psychiatry and Mental Health |
