Journal Article

FZJ-2018-07481

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Shared genetic etiology between alcohol dependence and major depressive disorder.

Foo, J. C. (Corresponding author) ; Streit, F. (Corresponding author) ; Treutlein, J. ; Ripke, S. ; Witt, S. H. ; Strohmaier, J. ; Degenhardt, F. ; Forstner, A. J. ; Hoffmann, P. ; Soyka, M. ; Dahmen, N. ; Scherbaum, N. ; Wodarz, N. ; Heilmann-Heimbach, S. ; Herms, S. ; Cichon, S.FZJ* ; Preuss, U. ; Gaebel, W. ; Ridinger, M. ; Hoffmann, S. ; Schulze, T. G. ; Maier, W. ; Zill, P. ; Müller-Myhsok, B. ; Ising, M. ; Lucae, S. ; Nöthen, M. M. ; Mann, K. ; Kiefer, F. ; Rietschel, M. ; Frank, J. ; Consortium, M. D. D. W. G. o. t. P. G. (Collaboration Author)

2018
Lippincott Williams & Wilkins Hagerstown, Md.

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Please use a persistent id in citations: http://hdl.handle.net/2128/20950  doi:10.1097/YPG.0000000000000201

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.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. 571 - Connectivity and Activity (POF3-571) (POF3-571)

Appears in the scientific report 2018

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Database coverage:
; ; Allianz-Lizenz ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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