Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and ...chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.
Abstract
Short sleep duration has been linked to negative health effects, but is a complex phenotype with many contributing factors, including genetic. We evaluated 27 common single nucleotide ...polymorphisms (SNPs) in candidate genes previously reported to be associated with other sleep variables for association with self-reported habitual sleep duration in the UK Biobank in 111 975 individuals of European ancestry. Genetic variation in DAT1 (rs464049) was significantly associated with sleep duration after correction for multiple testing (p = 4.00 × 10−5), whereas SNPs correlated to a previously studied variable number tandem repeat (VNTR) in DAT1 were not significant in this population. We also replicated a previously reported association in DRD2. Independent replication of these associations and a second signal in DRD2 (rs11214607) was observed in an additional 261 870 participants of European ancestry from the UK Biobank. Meta-analysis confirmed genome-wide significant association of DAT1 rs464049 (G, beta standard error, SE = −0.96 0.18 minutes/allele, p = 5.71 × 10−10) and study-wide significant association of DRD2 (rs17601612, C, beta SE = −0.66 0.18 minutes/allele, p = 1.77 × 10−5; rs11214607, C, beta SE = 1.08 (0.24) minutes/allele, p = 1.39 × 10−6). Overall, SNPs in two dopamine-related genes were significantly associated with sleep duration, highlighting the important link of the dopamine system with adult sleep duration in humans.
Over the last decade, health mobile apps have become an increasingly popular tool used by clinicians and researchers to track food consumption and exercise. However, many consumer apps lack the ...technological features for facilitating the capture of critical food timing details.
This study aimed to introduce users to 11 apps from US app stores that recorded both dietary intake and food timing to establish which one would be the most appropriate for clinical research.
To determine a viable app that recorded both dietary intake and food timing for use in a food timing-related clinical study, we evaluated the time stamp data, usability, privacy policies, the accuracy of nutrient estimates, and general features of 11 mobile apps for dietary assessment that were available on US app stores. The following apps were selected using a keyword search of related terms and reviewed: text entry apps-Cronometer, DiaryNutrition, DietDiary, FoodDiary, Macros, and MyPlate; image entry apps-FoodView and MealLogger; and text plus image entry apps-Bitesnap, myCircadianClock, and MyFitnessPal.
Our primary goal was to identify apps that recorded food time stamps, which 8 (73%) of the 11 reviewed apps did. Of the 11 apps, only 4 (36%) allowed users to edit the time stamps. Next, we sought to evaluate the usability of the apps using the System Usability Scale across 2 days, and 82% (9/11) of the apps received favorable scores for usability. To enable use in research and clinical settings, the privacy policies of each app were systematically reviewed using common criteria, with 1 (9%) Health Insurance Portability and Accountability Act-compliant app (Cronometer). Furthermore, protected health information was collected by 9 (82%) of the 11 apps. Finally, to assess the accuracy of the nutrient estimates generated by these apps, we selected 4 sample food items and a 3-day dietary record to input into each app. The caloric and macronutrient estimates of the apps were compared with the nutrient estimates provided by a registered dietitian using the Nutrition Data System for Research database. In terms of the 3-day food record, the apps were found to consistently underestimate daily calories and macronutrients compared with the Nutrition Data System for Research output.
Overall, we found that the Bitesnap app provided flexible dietary and food timing functionality capable of being used in research and clinical settings, whereas most other apps lacked in the necessary food timing functionality or user privacy.
Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute ...substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (r
= 0.29, P = 1.90 × 10
) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): r
= 0.20, P = 3.12 × 10
; waist circumference: r
= 0.20, P = 2.12 × 10
).
The measurement of circulating levels of brain-derived neurotrophic factor (BDNF) has been proposed to be a marker of disease and an indicator of recovery. Thus, knowing the temporal pattern and ...influence of potential circadian rhythms is important. Although several studies have measured BDNF at different times of day, no studies have done so while controlling for potential masking influences such as sleep and activity. Further, no previous study has examined circadian rhythms within individuals. We examined circadian rhythms in plasma BDNF while minimizing masking from behavioral and environmental factors using a 30-h constant routine (CR) protocol. In a sample of 39 healthy adults, we found significant circadian rhythms in 75% of women and 52% of men. The timing of the acrophase of the BDNF rhythm, however, was unrelated to clock time in women, while it was related to clock time in men. These results indicate that the use of single-sample measures of plasma BDNF as a marker of disease will be unreliable, especially in women. Repeated plasma BDNF samples over a 24-h period within individuals would be needed to reveal abnormalities related to disease states.
The Circadia Study (Circadia) is a novel "direct-to-participant" research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. ...The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.
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