In:
Journal of Sleep Research, Wiley, Vol. 23, No. 6 ( 2014-12), p. 609-618
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 F innish 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 PCDH 7 ‐ CENTD 1 ( P = 0.011) and rs2031573 near KLF 6 ( P = 0.044). The risk alleles for shorter sleep (rs2031573 and rs1037079) were also associated with higher KLF 6 and PCDH 7 expression levels ( P 〈 0.05). Experimental sleep restriction increased the expression of KLF 6 ( P 〈 0.01). These data suggest that rs2031573 near KLF 6 or related loci and rs1037079 between PCDH 7‐ CENTD 1 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 KLF 6 and PCDH 7 in sleep regulation.
Type of Medium:
Online Resource
ISSN:
0962-1105
,
1365-2869
DOI:
10.1111/jsr.2014.23.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2007459-1
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