Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_FC5E04F06657
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts.
Périodique
Biological psychiatry
Auteur(s)
Zhang X., Abdellaoui A., Rucker J., de Jong S., Potash J.B., Weissman M.M., Shi J., Knowles J.A., Pato C., Pato M., Sobell J., Smit J.H., Hottenga J.J., de Geus EJC, Lewis C.M., Buttenschøn H.N., Craddock N., Jones I., Jones L., McGuffin P., Mors O., Owen M.J., Preisig M., Rietschel M., Rice J.P., Rivera M., Uher R., Gejman P.V., Sanders A.R., Boomsma D., Penninx BWJH, Breen G., Levinson D.F.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Statut éditorial
Publié
Date de publication
15/06/2019
Peer-reviewed
Oui
Volume
85
Numéro
12
Pages
1065-1073
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Major depressive disorder (MDD) is moderately heritable, with a high prevalence and a presumed high heterogeneity. Copy number variants (CNVs) could contribute to the heritable component of risk, but the two previous genome-wide association studies of rare CNVs did not report significant findings.
In this meta-analysis of four cohorts (5780 patients and 6626 control subjects), we analyzed the association of MDD to 1) genome-wide burden of rare deletions and duplications, partitioned by length (<100 kb or >100 kb) and other characteristics, and 2) individual rare exonic CNVs and CNV regions.
Patients with MDD carried significantly more short deletions than control subjects (p = .0059) but not long deletions or short or long duplications. The confidence interval for long deletions overlapped with that for short deletions, but long deletions were 70% less frequent genome-wide, reducing the power to detect increased burden. The increased burden of short deletions was primarily in intergenic regions. Short deletions in cases were also modestly enriched for high-confidence enhancer regions. No individual CNV achieved thresholds for suggestive or significant association after genome-wide correction. p values < .01 were observed for 15q11.2 duplications (TUBGCP5, CYFIP1, NIPA1, and NIPA2), deletions in or near PRKN or MSR1, and exonic duplications of ATG5.
The increased burden of short deletions in patients with MDD suggests that rare CNVs increase the risk of MDD by disrupting regulatory regions. Results for longer deletions were less clear, but no large effects were observed for long multigenic CNVs (as seen in schizophrenia and autism). Further studies with larger sample sizes are warranted.
Mots-clé
Copy number variation, Genetics, Genome-wide association study, Major depressive disorder, Meta-analysis, Neuroscience
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/05/2019 11:46
Dernière modification de la notice
20/08/2019 17:27
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