SpringerLink
Log in

The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders

  • Review
  • Published:
Current Sleep Medicine Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Insomnia has a bi-directional relationship with both psychiatric and addictive disorders, and recent twin studies have shown an overlap in the genetic risk between insomnia and these conditions. Given the multiple single nucleotide polymorphisms (SNPs) identified with small effect sizes in prior genome-wide association studies (GWAS), a polygenic risk score (PRS) estimates the disorder’s overall genetic risk using these SNPs. This narrative review evaluates the emerging data on the relationship between the genetic risk for insomnia and these disorders.

Recent Findings

The studies show that PRS of insomnia is positively associated with sleep disturbance symptoms, alcohol use disorder, marijuana use, and obsessive-compulsive disorder.

Summary

This emerging evidence shows a shared genetic risk between insomnia and these disorders. Future studies should compute insomnia PRS with larger sample sizes, elaborate on how the PRS interacts with other risk factors for disease, and identify underlying subtypes of these disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

No datasets were generated or analysed during the current study.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Roth T, Coulouvrat C, Hajak G, Lakoma MD, Sampson NA, Shahly V, et al. Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition criteria: results from the America Insomnia Survey. Biol Psychiatry. 2011;69(6):592–600.

    Article  PubMed  Google Scholar 

  2. Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems. Sleep. 2007;30(2):213–8.

    Article  PubMed  Google Scholar 

  3. Baglioni C, Battagliese G, Feige B, Spiegelhalder K, Nissen C, Voderholzer U, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord. 2011;135(1-3):10–9.

    Article  PubMed  Google Scholar 

  4. Perlis ML, Giles DE, Buysse DJ, Tu X, Kupfer DJ. Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord. 1997;42(2-3):209–12.

    Article  CAS  PubMed  Google Scholar 

  5. Pigeon WR, Hegel M, Unutzer J, Fan MY, Sateia MJ, Lyness JM, et al. Is insomnia a perpetuating factor for late-life depression in the IMPACT cohort? Sleep. 2008;31(4):481–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Barclay NL, Kocevska D, Bramer WM, Van Someren EJW, Gehrman P. The heritability of insomnia: a meta-analysis of twin studies. Genes Brain Behav. 2021;20(4):e12717.

    Article  CAS  PubMed  Google Scholar 

  7. •• Jansen PR, Watanabe K, Stringer S, Skene N, Bryois J, Hammerschlag AR, et al. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nat Genet. 2019;51(3):394–403. This is the largest published insomnia GWAS to date.

    Article  CAS  PubMed  Google Scholar 

  8. • Lane JM, Jones SE, Dashti HS, Wood AR, Aragam KG, van Hees VT, et al. Biological and clinical insights from genetics of insomnia symptoms. Nat Genet. 2019;51(3):387–93. This study conducted in-depth analyses of the association between genetic risk for insomnia and risk for psychiatric disorders.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, et al. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nat Commun. 2019;10(1):1499.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Vrieze SI, McGue M, Miller MB, Hicks BM, Iacono WG. Three mutually informative ways to understand the genetic relationships among behavioral disinhibition, alcohol use, drug use, nicotine use/dependence, and their co-occurrence: twin biometry, GCTA, and genome-wide scoring. Behav Genet. 2013;43(2):97–107.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gehrman PR, Meltzer LJ, Moore M, Pack AI, Perlis ML, Eaves LJ, Silberg JL. Heritability of insomnia symptoms in youth and their relationship to depression and anxiety. Sleep. 2011;34(12):1641–6.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lind MJ, Gehrman PR. Genetic pathways to insomnia. Brain Sci. 2016;6:4.

    Article  Google Scholar 

  13. Veatch OJ, Keenan BT, Gehrman PR, Malow BA, Pack AI. Pleiotropic genetic effects influencing sleep and neurological disorders. Lancet Neurol. 2017;16(2):158–70.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ban HJ, Kim SC, Seo J, Kang HB, Choi JK. Genetic and metabolic characterization of insomnia. PloS One. 2011;6(4):e18455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Byrne EM, Gehrman PR, Medland SE, Nyholt DR, Heath AC, Madden PA, et al. A genome-wide association study of sleep habits and insomnia. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(5):439–51.

    Article  PubMed  Google Scholar 

  16. Hammerschlag AR, Stringer S, de Leeuw CA, Sniekers S, Taskesen E, Watanabe K, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017;49(11):1584–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jansen PR, Watanabe K, Stringer S, Skene N, Bryois J, Hammerschlag AR, et al. Genome-wide analysis of insomnia (N=1,331,010) identifies novel loci and functional pathways. https://www.biorxivorg/content/101101/214973v2.2019.

  18. Watanabe K, Jansen PR, Savage JE, Nandakumar P, Wang X, Me Research T, et al. Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways. Nat Genet. 2022;54(8):1125–32.

    Article  CAS  PubMed  Google Scholar 

  19. Choi SW, Mak TS, O'Reilly PF. Tutorial: a guide to performing polygenic risk score analyses. Nat Protoc. 2020;15(9):2759–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018;19(9):581–90.

    Article  CAS  PubMed  Google Scholar 

  21. Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk. Nat Genet. 2019;51(3):404–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kocevska D, Trajanoska K, Mulder RH, Koopman-Verhoeff ME, Luik AI, Tiemeier H, van Someren EJW. Are some children genetically predisposed to poor sleep? A polygenic risk study in the general population. J Child Psychol Psychiatry. 2023. https://doi.org/10.1111/jcpp.13899.

    Article  PubMed  Google Scholar 

  23. Ma T, Chen H, Lu Q, Tong X. Polygenic risk for insomnia in adolescents of diverse ancestry. Front Genet. 2021;12:654717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Koshmanova E, Muto V, Chylinski D, Mouraux C, Reyt M, Grinard M, et al. Genetic risk for insomnia is associated with objective sleep measures in young and healthy good sleepers. Neurobiol Dis. 2022;175:105924.

    Article  PubMed  Google Scholar 

  25. • Chakravorty S, Kember RL, Mazzotti DR, Dashti HS, Toikumo S, Gehrman PR, Kranzler HR. The relationship between alcohol- and sleep-related traits: results from polygenic risk score and Mendelian randomization analyses. Drug Alcohol Depend. 2023;251:110912. This is one of the first studies to examine polygenic risk between insomnia and alcohol use disorders.

    Article  CAS  PubMed  Google Scholar 

  26. Winiger EA, Ellingson JM JM, Morrison CL, Corley RP, Pasman JA, Wall TL, et al. Sleep deficits and cannabis use behaviors: an analysis of shared genetics using linkage disequilibrium score regression and polygenic risk prediction. Sleep. 2021;44(3):zsaa188. https://doi.org/10.1093/sleep/zsaa188.

    Article  PubMed  Google Scholar 

  27. Forthman KL, Kuplicki R, Yeh HW, Khalsa SS, Paulus MP, Guinjoan SM. Transdiagnostic behavioral and genetic contributors to repetitive negative thinking: a machine learning approach. J Psychiatr Res. 2023;162:207–13.

    Article  PubMed  Google Scholar 

  28. Beaupre LMM, Tiwari AK, Golcalves VF, Zai CC, Marshe VS, Kewis CM, et al. Corrigendum: potential genetic overlap between insomnia and sleep symptoms in major depressive disorder: a polygenic risk score analysis. Front Psychiatry. 2022;13:893816.

    Article  Google Scholar 

  29. Strom NI, Grove J, Meier SM, Baekvad-Hansen M, Becker Nissen J, Damm Als T, et al. Polygenic heterogeneity across obsessive-compulsive disorder subgroups defined by a comorbid diagnosis. Front Genet. 2021;12:711624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Spielman A, Caruso L, Glovinsky P. A behavioral perspective on insomnia treatment. Psychiatr Clin North America. 1987;10:541–53.

    Article  CAS  Google Scholar 

  31. Hauri P, Olmstead E. Childhood-onset insomnia. Sleep. 1980;3(1):59–65.

    Article  CAS  PubMed  Google Scholar 

  32. Kranzler HR, Davis CN, Feinn R, **wala Z, Khan Y, Oikonomou A, et al. Adverse childhood events, mood and anxiety disorders, and substance dependence: gene x environment effects and moderated mediation. medRxiv. 2023. https://www.medrxiv.org/content/10.1101/2023.10.24.23297419v1

Download references

Funding

This work was supported by the following grants: I01 CX001957 (S.C.), 1K01LM012870 (O.J.V.), 5R21HD107535 (O.J.V.), R01 HL143790 (P.R.G), and R01 NR018836 (P.R.G.).

Author information

Authors and Affiliations

  1. Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, 3535 Market Street, Suite 670, Philadelphia, PA, 19104, USA

    Subhajit Chakravorty & Philip R. Gehrman

  2. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA

    Subhajit Chakravorty & Philip R. Gehrman

  3. Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA

    Olivia J. Veatch & Diego R. Mazzotti

Authors
  1. Subhajit Chakravorty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olivia J. Veatch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diego R. Mazzotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philip R. Gehrman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the writing of manuscript. All authors reviewed the final manuscript. S.C. prepared the Figures.

Corresponding author

Correspondence to Philip R. Gehrman.

Ethics declarations

Competing interests

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

No animal or human subjects by the authors were used in this study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chakravorty, S., Veatch, O.J., Mazzotti, D.R. et al. The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders. Curr Sleep Medicine Rep 10, 132–138 (2024). https://doi.org/10.1007/s40675-024-00288-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40675-024-00288-7

Keywords

Search

Navigation