Item type: | Article | ||||
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Journal or Publication Title: | Psychiatric Genetics | ||||
Publisher: | Lippincott | ||||
Place of Publication: | PHILADELPHIA | ||||
Volume: | 28 | ||||
Number of Issue or Book Chapter: | 4 | ||||
Page Range: | pp. 66-70 | ||||
Date: | 2018 | ||||
Institutions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie | ||||
Identification Number: |
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Keywords: | GENOME-WIDE ASSOCIATION; RISK; SCHIZOPHRENIA; COMORBIDITY; SCORES; alcohol dependence; disease comorbidity; genome-wide association studies; major depressive disorder; polygenic risk scores; psychiatric genomics consortium | ||||
Dewey Decimal Classification: | UNSPECIFIED | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Yes | ||||
Item ID: | 46922 |
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 ...
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 (approximate to 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-2=0.533%) and PGC-MDD1 (P-threshold=0.2, P=0.00014, R-2=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-2=1.34%) versus PGC-MDD1 (P-threshold=1.0, P=0.0013, R-2=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-2=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-2=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.
Metadata last modified: 28 Jul 2021 17:09