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Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits
Open accessAbstract
Danielle Posthuma and colleagues report a genome-wide association analysis for insomnia complaints in 113,006 individuals from the UK Biobank that identifies associations with variants near seven genes. They find evidence for sex-specific genetic architectures underlying genetic risk for insomnia and genetic correlations between insomnia complaints and psychiatric and metabolic traits. Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10−8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.
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“Recent GWAS have also reported common variants that are associated with sleep duration in UK Biobank10–12.”
From GWAS identifies 14 loci for device-measured physical activity and sleep duration (2018) · cites this paper as [10]
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Metadata
- Authors
- Hammerschlag, A. R., Stringer, S., de Leeuw, C. A., Sniekers, S., Taskesen, E., Watanabe, K., Blanken, T. F., Dekker, K., te Lindert, B. H. W., Wassing, R., Jonsdottir, I., Thorleifsson, G., Stefansson, H., Gislason, T., Berger, K., Schormair, B., Wellmann, J., Winkelmann, J., Stefansson, K., Oexle, K., Van Someren, E. J. W., & Posthuma, D.
- Affiliations
- Amsterdam Neuroscience (NL)
- Netherlands Institute for Neuroscience (NL)
- University of Münster (DE)
- Helmholtz Munich (DE)
- TUM Klinikum (DE)
- ORCID
- Venue
- Nature Genetics
- Published
- 2017-06-12
- Volume
- 49
- Issue
- 11
- Pages
- 1584-1592
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5600256
- OpenAlex
- W2621853784
- Cited by
- 289
- References
- 65
- Citations by year
- 2026: 14 · 2025: 35 · 2024: 24 · 2023: 28 · 2022: 34 · 2021: 35 · 2020: 37 · 2019: 41 · 2018: 34 · 2017: 6
- FWCI
- 42.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (480- 05-003, 433-09-228, 453.07.001, 453-14-005)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- genetic susceptibility loci, MEIS1, restless legs syndrome, pleiotropy, genetic correlation, metabolic phenotypes, subjective well-being, educational attainment, UK Biobank
- MeSH terms
- Myeloid Ecotropic Viral Integration Site 1 Protein, Adult, Alleles, Chromosome Mapping, Educational Status, Female, Gene Frequency, Humans, Sleep Initiation and Maintenance Disorders, Male, Neoplasm Proteins, Quality of Life, Restless Legs Syndrome, Sex Factors, Gene Expression, Genome, Human, Homeodomain Proteins, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Protein Interaction Mapping, Gene Regulatory Networks, Genome-Wide Association Study, Genetic Loci, Type D Personality
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