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J Sleep Res. 2014 Dec;23(6):609-618. doi: 10.1111/jsr.12175. Epub 2014 Aug 11.

Genome-wide association study of sleep duration in the Finnish population.

Author information

1
Public Health Genomics Unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.
2
Institute of Biomedicine, Physiology, University of Helsinki, Helsinki, Finland.
3
Department of Psychiatry, University of Helsinki, Helsinki, Finland.
4
The Wellcome Trust Sanger Institute, Cambridge, UK.
5
Population Studies Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.
6
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
7
Folkhälsan Research Centre, Helsinki, Finland.
8
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
9
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
10
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
11
Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
12
Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
13
Vasa Central Hospital, Vasa, Finland.
14
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
15
Department of Public Health, Hjelt Institute University of Helsinki, Helsinki, Finland.
16
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
17
Research Centre of Applied and Preventive Cardiovascular Medicine and the Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.
18
Department of Clinical Chemistry, Fimlab Laboratories and Tampere University School of Medicine, Tampere, Finland.
19
Working Hours, Alertness and Professional Traffic Team, Finnish Institute of Occupational Health, Helsinki, Finland.

Abstract

Sleep duration is genetically regulated, but the genetic variants are largely unknown. We aimed to identify such genes using a genome-wide association study (GWAS) combined with RNA expression at the population level, and with experimental verification. A GWAS was performed in a Finnish sample (n = 1941), and variants with suggestive association (P < 5 × 10(-5) ) were tested in a follow-up sample from the same population with sleep duration (n = 6834) and time in bed (n = 1720). Variants with pointwise association of P < 0.05 in the follow-up sample were analysed further. First, we correlated genotypes with transcript expression levels with sleep duration (n = 207). The expression levels of significant transcripts were further studied in experimental sleep restriction. Of the 31 variants with P < 5 × 10(-5) in the discovery sample, three variants showed nominal allelic association (P < 0.05) in the follow-up sample: rs10914351, near PTPRU (P = 0.049), rs1037079 in PCDH7-CENTD1 (P = 0.011) and rs2031573 near KLF6 (P = 0.044). The risk alleles for shorter sleep (rs2031573 and rs1037079) were also associated with higher KLF6 and PCDH7 expression levels (P < 0.05). Experimental sleep restriction increased the expression of KLF6 (P < 0.01). These data suggest that rs2031573 near KLF6 or related loci and rs1037079 between PCDH7-CENTD1 or related loci may contribute to the regulation of sleep duration via gene expression. These results illustrate the utility of combining different analytical approaches to identify genetic determinants for traits related to sleep physiology. However, additional studies are needed in order to understand the roles of KLF6 and PCDH7 in sleep regulation.

KEYWORDS:

RNA expression; genome-wide association; single nucleotide polymorphism; sleep duration; sleep restriction

PMID:
25109461
DOI:
10.1111/jsr.12175
[Indexed for MEDLINE]
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