Top

Current Sleep Medicine Reports

Published in:

02-03-2024 | Insomnia | Review

The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders

Authors: Subhajit Chakravorty, Olivia J. Veatch, Diego R. Mazzotti, Philip R. Gehrman

Published in: Current Sleep Medicine Reports | Issue 2/2024

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.

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

•• 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.CrossRefPubMed

• 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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

12.

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

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.CrossRefPubMedPubMedCentral

14.

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

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

19.

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

20.

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

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

23.

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

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMedPubMedCentral

30.

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

31.

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

32.

Kranzler HR, Davis CN, Feinn R, Jinwala 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

Title: The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders
Authors: Subhajit Chakravorty
Olivia J. Veatch
Diego R. Mazzotti
Philip R. Gehrman
Publication date: 02-03-2024
Publisher: Springer International Publishing
Keyword: Insomnia
Published in: Current Sleep Medicine Reports / Issue 2/2024
Electronic ISSN: 2198-6401
DOI: https://doi.org/10.1007/s40675-024-00288-7

At a glance: The STEP trials

Springer Medicine

The Relationship Between Genetic Risk for Insomnia and Psychiatric Disorders

Abstract

Purpose of Review

Recent Findings

Summary

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 2/2024

Internal Consistency and Test–Retest Reliability of the Jenkins Sleep Scale Across International Versions: A Reliability Generalization Meta-analysis

Insomnia and the Orexinergic Pathway in the Link with Psychopathology: Effects of DORAs in Insomnia Comorbid with Mental Disturbances

Associations Between Six Core Processes of Psychological Flexibility with Poor Sleep Outcomes: A Systematic Review and Meta-Analysis

CPAP Treatment in Resistant Hypertension

Electrophysiological Mechanisms of Memory Consolidation in Human Non-rapid Eye Movement Sleep

Emerging Technologies and Wearables for Monitoring and Managing Sleep Disorders in Patients with Cardiovascular Disease