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Potential Genetic Overlap Between Insomnia and Sleep Symptoms in Major Depressive Disorder: A Polygenic Risk Score Analysis

Melhuish Beaupre, L.M., Tiwari, A.K., Gonçalves, V.F., Zai, C.C., Marshe, V.S., Lewis, C.M., Martin, N.G., McIntosh, A.M., Adams, M.J., Baune, B.T., Levinson, D.F., Boomsma, D.I., Penninx, B.W.J.H., Breen, G., Hamilton, S., Awasthi, S., Ripke, S., Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, Jones, I., Byrne, E.M., Hickie, I.B., Potash, J.P., Shi, J., Weissman, M.M., Milaneschi, Y., Shyn, S.I., de Geus, E.J.C, Willemsen, G., Brown, G.M., Kennedy, J.L. and Major Depressive Disorder Working Group, (2021) Potential Genetic Overlap Between Insomnia and Sleep Symptoms in Major Depressive Disorder: A Polygenic Risk Score Analysis. Frontiers in Psychiatry, 12. p. 2118. ISSN Online: 1664-0640

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Abstract

Background: The prevalence of insomnia and hypersomnia in depressed individuals is substantially higher than that found in the general population. Unfortunately, these concurrent sleep problems can have profound effects on the disease course. Although the full biology of sleep remains to be elucidated, a recent genome-wide association (GWAS) of insomnia, and other sleep traits in over 1 million individuals was recently published and provides many promising hits for genetics of insomnia in a population-based sample.

Methods: Using data from the largest available GWAS of insomnia and other sleep traits, we sought to test if sleep variable PRS scores derived from population-based studies predicted sleep variables in samples of depressed cases [Psychiatric Genomics Consortium - Major Depressive Disorder subjects (PGC MDD)]. A leave-one-out analysis was performed to determine the effects that each individual study had on our results.

Results: The only significant finding was for insomnia, where p-value threshold, p = 0.05 was associated with insomnia in our PGC MDD sample (R2 = 1.75−3, p = 0.006).

Conclusion: Our results reveal that <1% of variance is explained by the variants that cover the two significant p-value thresholds, which is in line with the fact that depression and insomnia are both polygenic disorders. To the best of our knowledge, this is the first study to investigate genetic overlap between the general population and a depression sample for insomnia, which has important treatment implications, such as leading to novel drug targets in future research efforts.

Item Type: Article
Additional Information:

Copyright © 2021 Melhuish Beaupre, Tiwari, Gonçalves, Zai, Marshe, Lewis, Martin,
McIntosh, Adams, Baune, Levinson, Boomsma, Penninx, Breen, Hamilton, Awasthi,
Ripke, Jones, Jones, Byrne, Hickie, Potash, Shi, Weissman, Milaneschi, Shyn, Geus,
Willemsen, Brown, Kennedy and Major Depressive Disorder Working Group of
the Psychiatric Genomics Consortium. This is an open-access article distributed
under the terms of the Creative Commons Attribution License (CC BY). The use,
distribution or reproduction in other forums is permitted, provided the original
author(s) and the copyright owner(s) are credited and that the original publication
in this journal is cited, in accordance with accepted academic practice. No use,
distribution or reproduction is permitted which does not comply with these terms.

Funding:

This project was supported by the Frederick Banting and Charles
Best Canada Graduate Scholarship (LM), the Granville Nickerson
Fellowship in Pharmacogenetics (AT), Brain and Behavior
Research Foundation: NARSAD (AT), McLaughlin Centre
Accelerator Grant (2019-2020) (AT), CAMH Foundation (VG),
Brain and Behavior Research Foundation (NARSAD Young
Investigator) (VG), McLaughlin Centre Accelerator Grant (VG),
Larry and Judy Tanenbaum Foundation (JK). The NTR/NESDA
dataset was funded by the: Netherlands Organization for
Scientific Research (NWO) and MagW/ZonMW grants 904-
61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004,
463-06-001, 451-04-034, 400-05-717, Addiction-31160008,
Middelgroot-911-09-032, Spinozapremie 56-464-14192, Center
for Medical Systems Biology (CSMB, NWO Genomics),
Biobanking and Biomolecular Resources Research Infrastructure
(BBMRI–NL, 184.021.007); the European Science Foundation
(ESF, EU/QLRT-2001-01254), the European Community’s
Seventh Framework Program (FP7/2007-2013), ENGAGE
(HEALTH-F4-2007-201413); the European Science Council
(ERC Advanced, 230374), Rutgers University Cell and
DNA Repository (NIMH U24 MH068457-06), the Avera
Institute, Sioux Falls, South Dakota (USA) and the National
Institutes of Health (NIH, R01D0042157-01A, MH081802,
Grand Opportunity grants 1RC2 MH089951 and 1RC2
MH089995), the Netherlands Organization for Scientific
Research (Geestkracht program grant 10-000-1002); the Center
for Medical Systems Biology (CSMB, NWO Genomics),
Biobanking and Biomolecular Resources Research Infrastructure
(BBMRI-NL), VU University’s Institutes for Health and
Care Research (EMGO+) and Neuroscience Campus
Amsterdam, University Medical Center Groningen, Leiden
University Medical Center, National Institutes of Health (NIH,
R01D0042157-01A, MH081802, Grand Opportunity grants
1RC2 MH089951 and 1RC2 MH089995), Genetic Association
Information Network (GAIN) of the Foundation for the National
Institutes of Health. Computing was supported by BiG Grid,
the Dutch e-Science Grid, which was financially supported
by NWO.

Uncontrolled Discrete Keywords: sleep, major depressive disorder, insomnia,, hypersomnia,, polygenic risk
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:
Depositing User: Katherine Gordon-Smith
Date Deposited: 22 Dec 2021 17:53
Last Modified: 22 Dec 2021 17:53
URI: https://eprints.worc.ac.uk/id/eprint/11582

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