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Shared Genetic Etiology Between Alcohol Dependence and Major Depressive Disorder

Foo, J., Streit, F., Treutlein, J., Ripke, S., Witt, S., Strohmaier, J., Degenhardt, F., Forstner, A.J., Hoffmann, P., Soyka, M., Dahmen, N., Scherbaum, N., Wodarz, N., Heilmann-Heimbach, S., Herms, S., Cichon, S., Preuss, U., Gaebel, W., Major Depressive Disorder Working Group of the, Psychiatric Genomics Consortium, Jones, Lisa, 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. and Frank, J. (2018) Shared Genetic Etiology Between Alcohol Dependence and Major Depressive Disorder. Psychiatric genetics, 28 (4). pp. 66-70. ISSN 0955-8829

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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 PGCMDD1
(P-threshold=0.2, P=0.00014, R2=0.663%) metaanalyses;
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
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Uncontrolled Keywords: depression, alcohol dependence, major depressive disorder, genetics, genetics etiology, disease comorbidity, genome-wide association studies
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Copyright Info: Open Access
Depositing User: Katherine Gordon-Smith
Date Deposited: 12 Jul 2018 12:20
Last Modified: 05 Dec 2019 13:23
URI: https://eprints.worc.ac.uk/id/eprint/6890

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