• Medientyp: E-Artikel
  • Titel: Shared genetic etiology between alcohol dependence and major depressive disorder
  • Beteiligte: Foo, Jerome C [VerfasserIn]; Streit, Fabian [VerfasserIn]; Dahmen, Norbert [VerfasserIn]; Scherbaum, Norbert [VerfasserIn]; Wodarz, Norbert [VerfasserIn]; Heilmann-Heimbach, Stefanie [VerfasserIn]; Herms, Stefan [VerfasserIn]; Cichon, Sven [VerfasserIn]; Preuss, Ulrich [VerfasserIn]; Gaebel, Wolfgang [VerfasserIn]; Ridinger, Monika [VerfasserIn]; Hoffmann, Sabine [VerfasserIn]; Treutlein, Jens [VerfasserIn]; Schulze, Thomas G [VerfasserIn]; Maier, Wolfgang [VerfasserIn]; Zill, Peter [VerfasserIn]; Müller-Myhsok, Bertram [VerfasserIn]; Ising, Marcus [VerfasserIn]; Lucae, Susanne [VerfasserIn]; Nöthen, Markus M [VerfasserIn]; Mann, Karl [VerfasserIn]; Kiefer, Falk [VerfasserIn]; Rietschel, Marcella [VerfasserIn]; Ripke, Stephan [VerfasserIn]; [...]
  • Erschienen: Lippincott Williams & Wilkins, 2018
  • Erschienen in: Psychiatric genetics 28(4), 66-70 (2018). doi:10.1097/YPG.0000000000000201
  • Sprache: Englisch
  • DOI: https://doi.org/10.1097/YPG.0000000000000201
  • ISSN: 0955-8829; 1473-5873
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  • Beschreibung: 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.
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