scholarly journals Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

2016 ◽  
Author(s):  
Jacqueline M. Lane ◽  
Jingjing Liang ◽  
Irma Vlasac ◽  
Simon G. Anderson ◽  
David A. Bechtold ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Sleep Disturbances ◽  
Metabolic Diseases ◽  
Genome Wide Association ◽  
Association Analyses ◽  
Genome Wide ◽  
The Uk ◽  
Insomnia Symptoms

Chronic sleep disturbances, associated with cardio-metabolic diseases, psychiatric disorders and all-cause mortality1,2, affect 25–30% of adults worldwide3. While environmental factors contribute importantly to self-reported habitual sleep duration and disruption, these traits are heritable4–9, and gene identification should improve our understanding of sleep function, mechanisms linking sleep to disease, and development of novel therapies. We report single and multi-trait genome-wide association analyses (GWAS) of self-reported sleep duration, insomnia symptoms including difficulty initiating and/or maintaining sleep, and excessive daytime sleepiness in the UK Biobank (n=112,586), with discovery of loci for insomnia symptoms (near MEIS1, TMEM132E, CYCL1, TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR/OPHN1) and a composite sleep trait (near INADL and HCRTR2), as well as replication of a locus for sleep duration (at PAX-8). Genetic correlation was observed between longer sleep duration and schizophrenia (rG=0.29, p=1.90x10−13) and between increased excessive daytime sleepiness and increased adiposity traits (BMI rG=0.20, p=3.12x10−09; waist circumference rG=0.20, p=2.12x10−07).

scholarly journals Cardiovascular health and sleep disturbances in two population-based cohort studies

Heart ◽  
2019 ◽  
Vol 105 (19) ◽  
pp. 1500-1506 ◽  
Author(s):  
Nadine Hausler ◽  
Quentin Lisan ◽  
Thomas Van Sloten ◽  
Jose Haba-Rubio ◽  
Marie-Cécile Perier ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Sleep Disturbances ◽  
Cardiovascular Health ◽  
Heart Association ◽  
Relative Risk Ratio ◽  
Lower Odds ◽  
Ideal Metrics ◽  
Insomnia Symptoms

ObjectiveWe aimed to investigate the association between cardiovascular health (CVH), as defined by the American Heart Association, and several sleep disturbances.MethodsTwo community-based cohorts, the Paris Prospective Study 3 (PPS3, France, n=6441) and the CoLaus study (Switzerland, n=2989) were analysed. CVH includes 7 metrics which all can be classified as poor, intermediate and ideal. Global CVH score was categorised into poor (0–2 ideal metrics), intermediate (3–4 ideal metrics) and ideal (≥5 ideal metrics). Associations between global CVH and self-reported sleep disturbances (proxy of sleep-disordered breathing [SDB], excessive daytime sleepiness, insomnia symptoms and short/long sleep duration) and SDB severity measured by polysomnography (PSG) were investigated. Adjusted OR/relative risk ratio (RRR) and 95% CIs were estimated. Subjects with previous cardiovascular disease were excluded.ResultsCompared with poor CVH, subjects with intermediate and ideal global CVH had lower odds of self-reported SDB in both cohorts (ORs 0.55; 95% CI 0.44 to 0.68 and 0.35; 95% CI 0.22 to 0.53, respectively) and had lower SDB severity measured by PSG (RRR 0.07; 95% CI 0.02 to 0.20) in CoLaus. Subjects with intermediate and ideal global CVH had lower odds of excessive daytime sleepiness in PPS3 (ORs 0.82; 0.72 to 0.95 and 0.80; 0.82 to 1.02, respectively). No consistent associations were found between CVH and sleep duration or insomnia symptoms.ConclusionsHigher levels of CVH are associated with lower odds of SDB and excessive daytime sleepiness. However, causal interpretation cannot be made and associations might be bidirectional.

scholarly journals GWAS in 446,118 European adults identifies 78 genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

2018 ◽  
Author(s):  
Hassan S Dashti ◽  
Samuel E Jones ◽  
Andrew R Wood ◽  
Jacqueline M Lane ◽  
Vincent T. van Hees ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Brain Regions ◽  
Causal Link ◽  
European Ancestry ◽  
Association Analyses ◽  
Genome Wide ◽  
Synaptic Neurotransmission ◽  
Impact Accelerometer ◽  
The Uk ◽  
Genetic Contributions

AbstractSleep is an essential homeostatically-regulated state of decreased activity and alertness conserved across animal species, and both short and long sleep duration associate with chronic disease and all-cause mortality1,2. Defining genetic contributions to sleep duration could point to regulatory mechanisms and clarify causal disease relationships. Through genome-wide association analyses in 446,118 participants of European ancestry from the UK Biobank, we discover 78 loci for self-reported sleep duration that further impact accelerometer-derived measures of sleep duration, daytime inactivity duration, sleep efficiency and number of sleep bouts in a subgroup (n=85,499) with up to 7-day accelerometry. Associations are enriched for genes expressed in several brain regions, and for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission, catecholamine production, synaptic plasticity, and unsaturated fatty acid metabolism. Genetic correlation analysis indicates shared biological links between sleep duration and psychiatric, cognitive, anthropometric and metabolic traits and Mendelian randomization highlights a causal link of longer sleep with schizophrenia.

scholarly journals Sleep Duration and Excessive Daytime Sleepiness Are Associated with Obesity Independent of Diet and Physical Activity

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1219 ◽  
Author(s):  
Andrea Maugeri ◽  
Jose Medina-Inojosa ◽  
Sarka Kunzova ◽  
Antonella Agodi ◽  
Martina Barchitta ◽  
...  
Keyword(s):  
Physical Activity ◽  
Sleep Duration ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Central Obesity ◽  
Sleep Disturbances ◽  
Short Sleep Duration ◽  
Cross Sectional ◽  
Short Sleep ◽  
Diet And Physical Activity

In the European Union, Czech Republic ranks 3rd and 6th for the incidence of obesity and cardiovascular diseases, respectively. Worldwide, short sleep duration and excessive daytime sleepiness (EDS) characterize obese subjects, which in turn exhibit scarce physical activity and unhealthy diet. We aimed to understand the relationship between irregular sleep patterns, obesity and lifestyle factors, such as diet and physical activity, in a vulnerable Czech population. 1482 members of the Kardiovize cohort, a random sample of the Czech urban population, were included in a cross-sectional study. Exposure variables included self-reported sleep duration and EDS, assessed by the Epworth Sleepiness Scale. Primary outcomes were BMI and waist-to-hip ratio or prevalence of obesity and central obesity. Covariates included physical activity and diet. Associations and interactions between variables were evaluated using logistic regression analyses. After adjustment for covariates, short sleep duration (<7 h) was associated with greater odds of overweight (BMI > 25; OR = 1.42; 95%CI = 1.06–1.90; p = 0.020) and obesity (BMI > 30; OR = 1.40; 95%CI = 1.02–1.94; p = 0.047), while EDS was associated with greater odds of central obesity (OR = 1.72; 95%CI = 1.06–2.79; p = 0.030), independent of diet and physical activity. However, due to the cross-sectional nature of our study, further prospective, large-scale studies are needed to evaluate the etiological link and causality between sleep disturbances and obesity.

scholarly journals 1097 Sleep Disturbances, Sleep Burden, And Depressive Symptoms In US Hispanics/Latinos: Results From The HCHS/SOL Sueño Study

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A417-A418
Author(s):  
C Alcantara ◽  
M Wallace ◽  
D Sotres-Alvarez ◽  
C Vetter ◽  
A J Phillips ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Sleep Duration ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Sleep Disturbances ◽  
The United States ◽  
Sleep Efficiency ◽  
Sensitivity Analyses ◽  
Poor Sleep ◽  
Sleep Timing

Abstract Introduction While sleep disturbances and depression often co-occur, these associations are understudied among Hispanics/Latinos. We examined the associations of sleep disturbances and sleep burden with depressive symptoms among Hispanic/Latino adults in the United States. Methods We used cross-sectional data from the Hispanic Community Health Study/Study of Latinos Sueño Ancillary study (2010-2013). The study enrolled 2072 adults (ages 18-64; 51.5% females) who completed one-week wrist-actigraphy and sleep questionnaires. Sleep burden was operationalized as the total count of sleep disturbances across six domains (duration, efficiency, midpoint, variability, insomnia, sleepiness). Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale (CESD-10). We used weighted survey linear regressions to evaluate the association of sleep disturbances and sleep burden with elevated depressive symptoms (CESD≥10) in individual models adjusted for age, gender, site, heritage, nativity, education, income, and employment. Sensitivity analyses further adjusted for behavioral health risk factors and apnea-hypopnea index. Results An estimated 28.3% had elevated depressive symptoms, 8.0% had short sleep duration (&lt;6 hours of sleep), 10.9% had long sleep duration (&gt;9 hours), 45.2% exhibited a later sleep midpoint (≥4:00AM), 38.4% had high sleep timing variability (upper third tertile for between day sleep midpoint), 15.3% had insomnia (ISI≥10), 17.3% had excessive daytime sleepiness (ESS ≥10), 21.5% had poor sleep efficiency (&lt;85%), and 77.4% had a total sleep burden count of ≥0. Insomnia (ß=0.49,95%CI:.43,.56), later sleep timing (ß=0.10,95%CI:.04,.16), excessive daytime sleepiness (ß=0.19,95%CI:.11,.27), poor sleep efficiency (ß=0.09,95%CI:.02,.17), high variability (ß=0.07, 95%CI:.01,.12), and sleep burden (ß=0.11,95%CI:.09,.13), were each positively associated with elevated depressive symptoms in individual adjusted models and sensitivity analyses. Extreme sleep durations were not associated with elevated depressive symptoms. Conclusion Multiple inter-related sleep disturbances, particularly those pertaining to sleep quality and timing, are associated with depression and may be targets for future interventions aimed at improving mood among Hispanics/Latinos. Support HL127307, HL098927, HL125748

scholarly journals Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

PLoS Genetics ◽  
2016 ◽  
Vol 12 (8) ◽  
pp. e1006125 ◽  
Author(s):  
Samuel E. Jones ◽  
Jessica Tyrrell ◽  
Andrew R. Wood ◽  
Robin N. Beaumont ◽  
Katherine S. Ruth ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Genome Wide Association ◽  
Association Analyses ◽  
Genome Wide

scholarly journals Genome-wide association analyses in >119,000 individuals identifies thirteen morningness and two sleep duration loci

2016 ◽  
Author(s):  
Samuel E Jones ◽  
Jessica Tyrrell ◽  
Andrew R Wood ◽  
Robin N Beaumont ◽  
Katherine S Ruth ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Circadian Rhythms ◽  
Sleep Duration ◽  
Association Studies ◽  
Genome Wide Association ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Association Analyses ◽  
Genome Wide

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but little is known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 White British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness [95%CI 1.15, 1.27], P=3x10-12) and PER2 (1.09 odds of morningness [95%CI 1.06, 1.12], P=4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,823 23andMe participants; thirteen of the chronotype signals remained significant at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. For sleep duration, we replicated one known signal in PAX8 (2.6 [95%CIs 1.9, 3.2] minutes per allele P=5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 [95% CI: 1.3, 2.7] minutes per allele, P=1.2x10-9; and 1.6 [95% CI: 1.1, 2.2] minutes per allele, P=7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG=0.056, P=0.048); undersleeping and BMI (rG=0.147, P=1x10-5) and oversleeping and BMI (rG=0.097, P=0.039), Mendelian Randomisation analyses provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study provides new insights into the biology of sleep and circadian rhythms in humans.

scholarly journals Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium

SLEEP ◽  
2016 ◽  
Vol 39 (10) ◽  
pp. 1859-1869 ◽  
Author(s):  
Marcella Marinelli ◽  
Irene Pappa ◽  
Mariona Bustamante ◽  
Carolina Bonilla ◽  
Carolina Bonilla ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Genome Wide Association ◽  
Association Analyses ◽  
Genome Wide

scholarly journals Genome-wide association analysis of excessive daytime sleepiness identifies 42 loci that suggest phenotypic subgroups

2018 ◽  
Author(s):  
Heming Wang ◽  
Jacqueline M Lane ◽  
Samuel E Jones ◽  
Hassan S Dashti ◽  
Hanna Ollila ◽  
...  
Keyword(s):  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Genetic Risk Score ◽  
Genetic Correlations ◽  
Functional Deficits ◽  
Genome Wide ◽  
Reproductive Ageing ◽  
Aggregate Effect ◽  
The Uk ◽  
Transmission Pathways

AbstractExcessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. We identified 42 loci for self-reported EDS in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirmed the aggregate effect of a genetic risk score of 42 SNPs on EDS in independent Scandinavian cohorts and on other sleep disorders (restless leg syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). Strong genetic correlations were also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing. EDS variants clustered into two predominant composite phenotypes - sleep propensity and sleep fragmentation - with the former showing stronger evidence for enriched expression in central nervous system tissues, suggesting two unique mechanistic pathways. Mendelian randomization analysis indicated that higher BMI is causally associated with EDS risk, but EDS does not appear to causally influence BMI.

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