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, E.J.C., Lewis, C.M., Buttenschøn, H.N., Craddock, N., Jones, I., Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, 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, B.W.J.H., Breen, G. and Levinson, D.F.
(2019)
Genome-wide Burden of Rare Short Deletions is Enriched in Major Depressive Disorder in Four Cohorts.
Biological Psychiatry, 85 (12).
pp. 1065-1073.
ISSN Online: 0006-3223
|
Text
Genome-wide Burden of Rare Short Deletions Xianglong Zhang et al.pdf - Published Version Download (187kB) | Preview |
Abstract
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. [Abstract copyright: Copyright © 2019 Society of Biological Psychiatry. All rights reserved.]
Item Type: | Article |
---|---|
Additional Information: | © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) The full-text of the online published article can be accessed via the official URL. |
Uncontrolled Discrete Keywords: | copy number variation, genetics, genome-wide association study, major depressive disorder, meta-analysis, neuroscience |
Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
Divisions: | College of Health, Life and Environmental Sciences > School of Allied Health and Community |
Related URLs: | |
Copyright Info: | Open access article |
SWORD Depositor: | Prof. Pub Router |
Depositing User: | Lisa Jones |
Date Deposited: | 04 May 2019 15:50 |
Last Modified: | 17 Jun 2020 17:29 |
URI: | https://eprints.worc.ac.uk/id/eprint/7945 |
Actions (login required)
![]() |
View Item |