Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution.
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UNIL restricted access
State: Public
Version: author
Serval ID
serval:BIB_52030F115734
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution.
Journal
Journal of Affective Disorders
ISSN
1573-2517 (Electronic)
ISSN-L
0165-0327
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
155
Pages
81-89
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD.
METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies.
RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly.
LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias.
CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.
METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies.
RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly.
LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias.
CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.
Pubmed
Web of science
Create date
14/01/2014 14:40
Last modification date
20/08/2019 14:07