Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Titel eines Journals oder einer Zeitschrift: | Psychiatric Genetics | ||||
Verlag: | Lippincott | ||||
Ort der Veröffentlichung: | PHILADELPHIA | ||||
Band: | 28 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 4 | ||||
Seitenbereich: | S. 66-70 | ||||
Datum: | 2018 | ||||
Institutionen: | Medizin > Lehrstuhl für Psychiatrie und Psychotherapie | ||||
Identifikationsnummer: |
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Stichwörter / 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-Dezimal-Klassifikation: | Nicht ausgewählt | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 46922 |
Zusammenfassung
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 ...
Zusammenfassung
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.
Metadaten zuletzt geändert: 28 Jul 2021 17:09