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Potential genetic overlap between insomnia and sleep symptoms in major depressive disorder: A polygenic risk score analysis

Melhuish Beaupre, Lindsay M., Tiwari, Arun K., Gonçalves, Vanessa F., Zai, Clement C., Marshe, Victoria S., Lewis, Cathryn M., Martin, Nicholas G., McIntosh, Andrew M., Adams, Mark J., Baune, Bernhard T., Levinson, Doug F., Boomsma, Dorret I., Penninx, Brenda W. J. H., Breen, Gerome, Hamilton, Steve, Awasthi, Swapnil, Ripke, Stephan, Jones, Lisa ORCID:, Jones, Ian ORCID:, Byrne, Enda M., Hickie, Ian B., Potash, James P., Shi, Jianxin, Weissman, Myrna M., Milaneschi, Yuri, Shyn, Stanley I., Geus, Eco J. C. de, Willemsen, Gonneke, Brown, Gregory M., Kennedy, James L. and Major Depressive Disorder Working Group of the Psychiatric Genom 2021. Potential genetic overlap between insomnia and sleep symptoms in major depressive disorder: A polygenic risk score analysis. Frontiers in Psychiatry 12 , 734077. 10.3389/fpsyt.2021.734077

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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
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:
Publisher: Frontiers Media
Date of First Compliant Deposit: 19 August 2022
Date of Acceptance: 1 November 2021
Last Modified: 11 Oct 2023 18:58

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