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Nat Genet. 2017 Nov;49(11):1584-1592. doi: 10.1038/ng.3888. Epub 2017 Jun 12.

Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.

Author information

1
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
2
Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
3
Department of Sleep and Cognition, Netherlands Institute for Neuroscience (an institute of the Royal Netherlands Academy of Arts and Sciences), Amsterdam, the Netherlands.
4
Department of Integrative Neurophysiology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
5
Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
6
deCODE Genetics, Amgen, Inc., Reykjavík, Iceland.
7
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
8
Department of Respiratory Medicine and Sleep, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland.
9
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
10
Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
11
Institute of Human Genetics, Technische Universität München, Munich, Germany.
12
Neurologische Klinik und Poliklinik, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany.
13
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
14
Department of Clinical Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.

Abstract

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.

PMID:
28604731
PMCID:
PMC5600256
DOI:
10.1038/ng.3888
[Indexed for MEDLINE]
Free PMC Article

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