Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Wang, Heming; Lane, Jacqueline M.; Jones, Samuel E.; Dashti, Hassan S.; Ollila, Hanna; Wood, Andrew R.; Hees, Vincent T. van; Brumpton, Ben; Winsvold, Bendik S.; Kantojärvi, Katri; Palviainen, Teemu; Cade, Brian E.; Sofer, Tamar; Song, Yanwei; Patel, Krunal; Anderson, Simon; Bechtold, David A.; Bowden, Jack; Emsley, Richard; Kyle, Simon D.; Little, Max A.; Loudon, A. S. I.; Scheer, Frank A.J.L.; Purcell, Shaun; Richmond, Rebecca C; Spiegelhalder, Kai; Tyrrell, Jessica; Zhu, Xiaofeng; Hublin, Christer; Kaprio, Jaakko; Kristiansson, Kati; Sulkava, Sonja; Paunio, Tiina; Hveem, Kristian; Nielsen, Jonas B.; Willer, Cristen J.; Zwart, John‐Anker; Strand, Linn Beate; Frayling, Timothy M.; Ray, David; Lawlor, Deborah A; Rutter, Martin K.; Weedon, Michael N.; Redline, Susan; Saxena, Richa

doi:10.1038/s41467-019-11456-7

Cited by 159 publications

(139 citation statements)

References 71 publications

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“…Sleep lengths in twins have been similar as in other Finnish studies [27]. In addition, our twin cohort has taken part in multiple genome-wide association studies, with cohort specific effect size estimates that do not differ from the metaanalysis results [35,36]. The results are also valuable from an ontogeny point of view.…”

Section: Discussionsupporting

confidence: 59%

Changes in self-reported sleep duration with age - a 36-year longitudinal study of Finnish adults

2020

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Background Sleep deprivation is often claimed to be increasingly common, but most studies show small changes in sleep duration over the last decades. Our aim was to analyze long-term patterns in self-reported sleep duration in a population-based cohort. Methods Members of the Older Finnish Twin Cohort have responded to questionnaires in 1975 (N = 30,915 individuals, response rate 89%, mean age 36 years), 1981 (24,535, 84%, 41 years), 1990 (12,450, 77%, 44 years), and 2011 (8334, 72%, 60 years). Weibull regression models were used to model the effects of follow-up time and age simultaneously. Results Sleep duration has decreased in all adult age groups and in both genders. The mean duration was in men 7.57 h in 1975 and 7.39 in 2011, and in women 7.69 and 7.37, respectively. The decrease was about 0.5 min in men and 0.9 in women per year of follow-up. In the age-group 18–34 years, mean sleep length was 7.69 h in 1975 and 7.53 in 1990. Among 35–54-year-old it was 7.57 h in 1975 and 7.34 in 2011, and in the age group of 55+ year olds 7.52 and 7.38, correspondingly. The change was largest in middle-aged group: about 23 min or about 0.6 min per year of follow-up. Conclusions There has been a slight decrease in mean sleep duration during the 36-year follow-up. Although the sleep duration was longer in 1970s and 1980s, the probable main cause for the change in this study population is the effect of aging.

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Section: Discussionsupporting

confidence: 59%

Changes in self-reported sleep duration with age - a 36-year longitudinal study of Finnish adults

2020

Self Cite

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show abstract

“…Sleep lengths in twins have been similar as in other Finnish studies [27]. In addition, our twin cohort has taken part in multiple genome-wide association studies, with cohort speci c effect size estimates that do not differ from the meta-analysis results [35,36]. The results are also valuable from an ontogeny point of view.…”

Section: Discussionsupporting

confidence: 57%

Changes In Self-Reported Sleep Duration With Age - A 36-Year Longitudinal Study Of Finnish Adults

Hublin

Haasio

Kaprio

2020

Preprint

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Background: Sleep deprivation is often claimed to be increasingly common, but most studies show small changes in sleep duration over the last decades. Our aim was to analyze long-term patterns in self-reported sleep duration in a population-based cohort. Methods: Members of the Older Finnish Twin Cohort have responded to questionnaires in 1975 (N = 30,915 individuals, response rate 89%, mean age 36 years), 1981 (24,506, 84%, 41 years), 1990 (12,502, 77%, 44 years), and 2011 (8510, 72%, 60 years). Weibull regression models were used to model the effects of follow-up time and age simultaneously. Results: Sleep duration has decreased in all adult age groups and in both genders. The mean duration was in men 7.57 hours in 1975 and 7.39 in 2011, and in women 7.69 and 7.37, respectively. The decrease was about 0.5 minutes in men and 0.9 in women per year of follow-up. In the age-group 18-34 years, mean sleep length was 7.69 hours in 1975 and 7.53 in 1990. Among 35-54-year-old it was 7.57 hours in 1975 and 7.34 in 2011, and in the age group of 55+ year olds 7.52 and 7.38, correspondingly. The change was largest in middle-aged group: about 23 minutes or about 0.6 minutes per year of follow-up. Conclusions: There has been a slight decrease in mean sleep duration during the 36-year follow-up. Although the sleep duration was longer in 1970s and 1980s, the probable main cause for the change in this study population is the effect of aging.

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“…Large cohorts of individuals assembled for human Genomewide Association Studies (GWAS) report significant phenotypic variation in typical sleep duration, timing, and quality [8][9][10][11]. Since a fraction of this variation is genetic in origin-for instance, the Single Nucleotide Polymorphism or SNP-based heritability of sleep duration has been estimated at 9.8% [8]-and because modern human GWAS employ hundreds of thousands of individuals, human geneticists have successfully identified, and in many cases replicated small-effect loci contributing to variation in sleep parameters in human populations.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Genetic Basis of Variation in Drosophila Sleep Using a Multiparental QTL Mapping Resource

Smith

Macdonald

2020

Genes

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There is considerable variation in sleep duration, timing and quality in human populations, and sleep dysregulation has been implicated as a risk factor for a range of health problems. Human sleep traits are known to be regulated by genetic factors, but also by an array of environmental and social factors. These uncontrolled, non-genetic effects complicate powerful identification of the loci contributing to sleep directly in humans. The model system, Drosophila melanogaster, exhibits a behavior that shows the hallmarks of mammalian sleep, and here we use a multitiered approach, encompassing high-resolution QTL mapping, expression QTL data, and functional validation with RNAi to investigate the genetic basis of sleep under highly controlled environmental conditions. We measured a battery of sleep phenotypes in >750 genotypes derived from a multiparental mapping panel and identified several, modest-effect QTL contributing to natural variation for sleep. Merging sleep QTL data with a large head transcriptome eQTL mapping dataset from the same population allowed us to refine the list of plausible candidate causative sleep loci. This set includes genes with previously characterized effects on sleep and circadian rhythms, in addition to novel candidates. Finally, we employed adult, nervous system-specific RNAi on the Dopa decarboxylase, dyschronic, and timeless genes, finding significant effects on sleep phenotypes for all three. The genes we resolve are strong candidates to harbor causative, regulatory variation contributing to sleep.

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Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Cited by 159 publications

References 71 publications

Changes in self-reported sleep duration with age - a 36-year longitudinal study of Finnish adults

Changes in self-reported sleep duration with age - a 36-year longitudinal study of Finnish adults

Changes In Self-Reported Sleep Duration With Age - A 36-Year Longitudinal Study Of Finnish Adults

Dissecting the Genetic Basis of Variation in Drosophila Sleep Using a Multiparental QTL Mapping Resource

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