Dataset Information

Genetic evidence for the causal effects of C-reactive protein on self-reported habitual sleep duration.

ABSTRACT: Inflammatory responses to acute stimuli are proposed to regulate sleep, but the relationship between chronic inflammation and habitual sleep duration is elusive. Here, we study this relation using genetically predicted level of chronic inflammation, indexed by CRP and IL6 signaling, and self-reported sleep duration. By Mendelian randomization analysis, we show that elevated CRP level within <10 mg/L has a homeostatic effect that facilitates maintaining 7-8 h sleep duration per day - making short-sleepers sleep longer (p = 2.42 × 10^-2) and long-sleepers sleep shorter (1.87 × 10^-7); but it is not associated with the overall sleep duration (p = 0.17). This homeostatic effect replicated in an independent CRP dataset. We observed causal effects of the soluble interleukin 6 receptor and gp130 on overall sleep duration (p = 1.62 × 10^-8, p = 2.61 × 10^-58, respectively), but these effects disappeared when CRP effects were accounted for in the model. Using polygenic score analysis, we found that the homeostatic effect of CRP on sleep duration stems primarily from the genetic variants within the CRP gene region: when genetic variants outside of this region were used to predict CRP levels, the opposite direction of effect was observed. In conclusion, we show that elevated CRP level may causally facilitate maintaining an optimal sleep duration that is beneficial to health, thus updating our current knowledge of immune regulation on sleep.

SUBMITTER: Iakunchykova O

PROVIDER: S-EPMC10950822 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic evidence for the causal effects of C-reactive protein on self-reported habitual sleep duration.

Iakunchykova Olena O Pan Mengyu M Amlien Inge K IK Roe James M JM Walhovd Kristine B KB Fjell Anders M AM Chen Chi-Hua CH Benros Michael E ME Wang Yunpeng Y

Brain, behavior, & immunity - health 20240311

Inflammatory responses to acute stimuli are proposed to regulate sleep, but the relationship between chronic inflammation and habitual sleep duration is elusive. Here, we study this relation using genetically predicted level of chronic inflammation, indexed by CRP and IL6 signaling, and self-reported sleep duration. By Mendelian randomization analysis, we show that elevated CRP level within <10 mg/L has a homeostatic effect that facilitates maintaining 7-8 h sleep duration per day - making short ...[more]

PMID: 38511149

Similar Datasets

Project description:BackgroundSelf-reported short or long sleep duration has been associated with adverse cardiometabolic health outcomes in laboratory and epidemiologic studies, but interpretation of such data has been limited by methodologic issues.MethodsAdult respondents of the 2007-2008 US National Health and Nutrition Examination Survey (NHANES) were examined in a cross-sectional analysis (N=5649). Self-reported sleep duration was categorized as very short (<5 h), short (5-6 h), normal (7-8 h), or long (≥9 h). Obesity, diabetes mellitus (DM), hypertension, and hyperlipidemia were objectively assessed by self-reported history. Statistical analyses included univariate comparisons across sleep duration categories for all variables. Binary logistic regression analyses and cardiometabolic factor as outcome, with sleep duration category as predictor, were assessed with and without covariates. Observed relationships were further assessed for dependence on race/ethnicity.ResultsIn adjusted analyses, very short sleep was associated with self-reported hypertension (odds ratio [OR], 2.02, [95% confidence interval {CI},1.45-2.81]; P<0.0001), self-reported hyperlipidemia (OR, 1.96 [95% CI, 1.43-2.69]; P<0.0001), objective hyperlipidemia (OR, 1.41 [95% CI, 1.04-1.91]; P=0.03), self-reported DM (OR, 1.76 [95% CI, 1.13-2.74]; P=0.01), and objective obesity (OR, 1.53 [95% CI, 1.03-1.43]; P=0.005). Regarding short sleep (5-6 h), in adjusted analyses, elevated risk was seen for self-reported hypertension (OR, 1.22 [95% CI, 1.02-1.45]; P=0.03) self-reported obesity (OR, 1.21 [95% CI, 1.03-1.43]; P=0.02), and objective obesity (OR, 1.17 [95% CI, 1.00-1.38]; P<0.05). Regarding long sleep (≥9 h), no elevated risk was found for any outcomes. Interactions with race/ethnicity were significant for all outcomes; race/ethnicity differences in patterns of risk varied by outcome studied. In particular, the relationship between very short sleep and obesity was strongest among blacks and the relationship between short sleep and hypertension is strongest among non-Hispanic whites, blacks, and non-Mexican Hispanics/Latinos.ConclusionsShort sleep duration is associated with self-reported and objectively determined adverse cardiometabolic outcomes, even after adjustment for many covariates. Also, these patterns of risk depend on race/ethnicity.

Project description:IntroductionCigarette smokers are at increased risk of poor sleep behaviors. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bidirectional).MethodsWe obtained summary-level data of genome-wide association studies of smoking (smoking initiation [n = 74 035], cigarettes per day [n = 38 181], and smoking cessation [n = 41 278]) and sleep behaviors (sleep duration and chronotype, or "morningness" [n = 128 266] and insomnia [n = 113 006]). Using linkage disequilibrium (LD) score regression, we calculated genetic correlations between smoking and sleep behaviors. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual-level data (n = 333 581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse variance-weighted meta-analysis, weighted median regression, MR-Robust Adjusted Profile Score, and MR Egger methods.ResultsWe found negative genetic correlations between smoking initiation and sleep duration (rg = -.14, 95% CI = -0.26 to -0.01) and smoking cessation and chronotype (rg = -.18, 95% CI = -0.31 to -0.06), and positive genetic correlations between smoking initiation and insomnia (rg = .27, 95% CI = 0.06 to 0.49) and cigarettes per day and insomnia (rg = .15, 95% CI = 0.01 to 0.28). MR provided strong evidence that smoking more cigarettes causally decreases the odds of being a morning person, (RAPS) and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds.ConclusionsSmoking and sleep behaviors show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target.ImplicationsUsing LD score regression, we found evidence that smoking and different sleep behaviors (sleep duration, chronotype (morningness), and insomnia) are moderately genetically correlated-genetic variants associated with less or poorer sleep also increased the odds of smoking (more heavily). MR analyses suggested that heavier smoking causally affects circadian rhythm (decreasing the odds of being a morning person) and there was some indication that insomnia increases smoking heaviness and hampers smoking cessation. Our findings indicate a complex, bidirectional relationship between smoking and sleep behaviors and point to sleep as a potentially interesting smoking treatment target.

Project description:ObjectivesTo advance understanding of the relationship between discrimination and sleep duration and difficulties, with consideration of multiple dimensions of discrimination, and attention to concurrent stressors; and to examine the contribution of discrimination and other stressors to racial/ ethnic differences in these outcomes.DesignCross-sectional probability sample.SettingChicago, IL.ParticipantsThere were 2,983 black, Hispanic, and white adults.Measurements and resultsOutcomes included self-reported sleep duration and difficulties. Discrimination, including racial and nonracial everyday and major experiences of discrimination, workplace harassment and incivilities, and other stressors were assessed via questionnaire. In models adjusted for sociodemographic characteristics, greater exposure to racial (? = -0.14)) and nonracial (? = -0.08) everyday discrimination, major experiences of discrimination attributed to race/ethnicity (? = -0.17), and workplace harassment and incivilities (? = -0.14) were associated with shorter sleep (P < 0.05). The association between major experiences of discrimination attributed to race/ethnicity and sleep duration (? = -0.09, P < 0.05) was independent of concurrent stressors (i.e., acute events, childhood adversity, and financial, community, employment, and relationship stressors). Racial (? = 0.04) and non-racial (? = 0.05) everyday discrimination and racial (? = 0.04) and nonracial (? = 0.04) major experiences of discrimination, and workplace harassment and incivilities (? = 0.04) were also associated with more (log) sleep difficulties, and associations between racial and nonracial everyday discrimination and sleep difficulties remained after adjustment for other stressors (P < 0.05). Racial/ethnic differences in sleep duration and difficulties were not significant after adjustment for discrimination (P > 0.05).ConclusionsDiscrimination was associated with shorter sleep and more sleep difficulties, independent of socioeconomic status and other stressors, and may account for some of the racial/ethnic differences in sleep.

Project description:Study objectivesWe examined whether interindividual differences in habitual sleep patterns, quantified as the cumulative habitual total sleep time (cTST) over a 2-w period, were reflected in waking measurements of intranetwork and internetwork functional connectivity (FC) between major nodes of three intrinsically connected networks (ICNs): default mode network (DMN), salience network (SN), and central executive network (CEN).MethodsResting state functional magnetic resonance imaging (fMRI) study using seed-based FC analysis combined with 14-d wrist actigraphy, sleep diaries, and subjective questionnaires (N = 33 healthy adults, mean age 34.3, standard deviation ± 11.6 y). Data were statistically analyzed using multiple linear regression. Fourteen consecutive days of wrist actigraphy in participant's home environment and fMRI scanning on day 14 at the Birmingham University Imaging Centre. Seed-based FC analysis on ICNs from resting-state fMRI data and multiple linear regression analysis performed for each ICN seed and target. cTST was used to predict FC (controlling for age).ResultscTST was specific predictor of intranetwork FC when the mesial prefrontal cortex (MPFC) region of the DMN was used as a seed for FC, with a positive correlation between FC and cTST observed. No significant relationship between FC and cTST was seen for any pair of nodes not including the MPFC. Internetwork FC between the DMN (MPFC) and SN (right anterior insula) was also predicted by cTST, with a negative correlation observed between FC and cTST.ConclusionsThis study improves understanding of the relationship between intranetwork and internetwork functional connectivity of intrinsically connected networks (ICNs) in relation to habitual sleep quality and duration. The cumulative amount of sleep that participants achieved over a 14-d period was significantly predictive of intranetwork and inter-network functional connectivity of ICNs, an observation that may underlie the link between sleep status and cognitive performance.

Project description:Study objectivesThis study aims to examine associations between acculturative stress-defined as the psychological impact, or stress reaction, of adapting to a new cultural context-and self-reported sleep outcomes among Chinese and Korean immigrants in the United States.MethodsIn this cross-sectional study, acculturative stress was assessed using a 9-item scale, and sleep disturbance was measured using the 8-item scale. Sleep duration was self-reported. Poisson and linear regression analyses were conducted to examine the associations between acculturative stress, sleep disturbance, and sleep duration.ResultsOur sample consists of 400 participants (females: 52%, Chinese: 50%, Koreans: 50%, the mean of age = 58.4). 81.8% of them were classified as having no sleep disturbance, whereas 18.2% were classified as having sleep disturbance. Poisson models revealed that greater acculturative stress was associated with a higher prevalence of sleep disturbance (Prevalence Ratio (PR): 1.18, 95% confidence interval (CI): 1.06% to 1.31%). In linear models, a one-unit increase in acculturative stress was associated with 0.08 hr less sleep (p < .05). Interaction tests indicated effect modification for sleep disturbance by sex and ethnic identity: only women had a significant association between acculturative stress and sleep disturbance (PR: 1.30; 95% CI: 1.13 to 1.49), while the association was significant for individuals identifying as "very Asian" (PR: 1.21; 95% CI: 1.08 to 1.35), but not for those identifying as "mostly Asian" or "bicultural/western".ConclusionsIf findings are replicated, we suggest developing intervention programs for Asian immigrants to minimize acculturative stress and bolster protective factors that decrease the risk for poor sleep outcomes.Information on Clinical Trial: Name: Screening To Prevent ColoRectal Cancer (STOP CRC) among At-Risk Asian American Primary Care Patients NCT Number: NCT03481296 URL: https://clinicaltrials.gov/ct2/show/NCT03481296?term=Sunmin+Lee&draw=2&rank=1.

Dataset Information

Genetic evidence for the causal effects of C-reactive protein on self-reported habitual sleep duration.

Publications

Genetic evidence for the causal effects of C-reactive protein on self-reported habitual sleep duration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets