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Nat Genet. 2019 Mar;51(3):394-403. doi: 10.1038/s41588-018-0333-3. Epub 2019 Feb 25.

Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways.

Author information

1
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.
2
Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
3
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
4
UCL Institute of Neurology, Queen Square, London, UK.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
6
Department of Social, Health and Organisational Psychology, Utrecht University, Utrecht, the Netherlands.
7
Department of Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, the Netherlands.
8
Department of Clinical Genetics, Section of Complex Trait Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
9
Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
10
23andMe, Inc., Mountain View, CA, USA.
11
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
12
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
13
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands.
14
Department of Sleep and Cognition, Netherlands Institute for Neuroscience (an institute of the Royal Netherlands Academy of Arts and Sciences), Amsterdam, The Netherlands.
15
Departments of Psychiatry and Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam University Medical Center, Amsterdam, The Netherlands.
16
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands. d.posthuma@vu.nl.
17
Department of Clinical Genetics, Section of Complex Trait Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands. d.posthuma@vu.nl.

Abstract

Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets.

PMID:
30804565
DOI:
10.1038/s41588-018-0333-3
[Indexed for MEDLINE]

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