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PubMed2026

Investigating the causal effects of physical activity and sedentary behavior on hernia risk: A two-sample Mendelian randomization approach.

The global prevalence of hernia is increasing, particularly due to the aging population. Although physical activity and sedentary behavior are known to influence various health outcomes, their specific roles in hernia development remain inadequately investigated. This study aimed to systematically assess the causal relationships between physical activity, sedentary behavior, and the risk of hernia development using Mendelian randomization (MR) analysis. We used genome-wide association study data from the UK Biobank and FinnGen Biobank to explore the causal effects of sedentary behavior on hernia risk via 5 distinct MR approaches. To ensure the reliability of our risk models, we performed sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Furthermore, we employed multivariable MR analysis to determine the independent causal effects of both physical activity and sedentary behavior. Our findings indicate that moderate-to-vigorous physical activity (MVPA) was significantly associated with an increased risk of inguinal hernia, with an odds ratio of 1.844 (95% confidence interval, 1.181-2.879; P = .007). Associations between sedentary behavior and diaphragmatic or umbilical hernia were inconsistent across methods and were sensitive to pleiotropy; thus, no robust causal relationship was established. Multivariable MR analysis further confirmed the independent and significant causal relationship between MVPA and inguinal hernia, with an odds ratio of 1.901 (95% confidence interval, 1.098-3.291; P = .022). Our study highlights a significant association between MVPA and an increased risk of inguinal hernia, suggesting that physical activity should be carefully considered in preventive strategies for hernias. However, the relationship between sedentary behavior and hernia development warrants further investigation.

Mendelian Randomization Analysis↗

PubMed2025

Education, socioeconomic status, leisure sedentary behaviors and female infertility: mendelian randomization study.

BACKGROUND: Previous studies have indicated that education, socioeconomic status, and leisure sedentary behavior may be associated with female infertility. However, it remains unclear whether these associations imply causal relationships. METHODS: Genetic variants from genome-wide association studies (GWAS) of education, socioeconomic status, and leisure sedentary behaviors were obtained from the UK Biobank and MRC-IEU database (Medical Research Council Integrative Epidemiology Unit), female infertility data was acquired from the FinnGen Biobank. Univariable and multivariable MR analyses were performed to explore the relationships between these traits and female infertility. RESULTS: The results of the univariate MR analysis indicated that age of full-time education had a protective effect on female infertility (odds ratio [OR] 0.471; 95% confidence interval [CI] 0.24 to 0.93; p = 0.03). Multivariable MR and reverse MR studies support the existence of a relationship between them. However, no causal correlation was found between other traits and female infertility. No significant heterogeneity or horizontal pleiotropy was detected, and the stability of the results was confirmed through sensitivity analysis and the leave-one-out test. CONCLUSIONS: A later age of completion of full-time education may be causally related to a reduced risk of female infertility, but no causality is established between other educational levels factors, socioeconomic status, or sedentary behaviors and infertility risk.

Humans↗

PubMed2024

Reassessing the Association of Sedentary Behavior and Physical Activity with Ischemic Stroke: A Mendelian Randomization Study.

PURPOSE: Findings from previous Mendelian randomization (MR) studies disagreed with the current scientific consensus regarding the role of physical activity (PA) and sedentary behavior in ischemic stroke (IS). We reassessed these associations with a focus on etiological subtypes of IS and the potential mediating roles of cardiometabolic traits and brain imaging-derived phenotypes (IDPs). METHODS: We performed MR analyses using summary statistics from genome-wide association studies of sedentary behavior and PA ( n = 88,411 ~ 608,595), cardiometabolic traits ( n = 393,193 ~ 694,649), brain IDPs ( n = 33,224), and the latest IS data (62,100 cases and 1,234,808 controls). Inverse-variance weighted regression was used as the primary method, complemented by several sensitivity analyses. A two-step MR approach was employed to assess the mediating effects of cardiometabolic traits and brain IDPs. RESULTS: Genetic liability to leisure-time moderate-to-vigorous PA (MVPA) and higher overall PA (OPA) were associated with reduced risks of IS and small vessel stroke (Benjamini-Hochberg adjusted P < 0.05). Suggestive associations were observed between longer leisure-screen time and higher IS risk and between higher OPA and lower cardioembolic stroke risk ( P < 0.05). The isotropic volume fraction in the anterior limb of the left internal capsule, as well as some cardiometabolic metrics, partially mediated these associations. There was no evidence for causal effects of overall MVPA, overall light-intensity PA, or overall sedentary duration on IS. CONCLUSIONS: Longer leisure screen time, less OPA, and not engaging in MVPA during leisure time were associated with higher risk of IS. The associations between PA and IS depended on different subtypes and were mediated by changes in anterior limb of the left internal capsule and cardiometabolic biomarkers.

Humans↗

PubMed1991

Smoking and sedentary behavior as related to work organization.

There is little research which has investigated whether working life may affect health behaviors. However, there is data suggesting that smoking as well as leisure activities are affected during times of stress. Both theoretical work and research suggests that work may socialize people such that the use of leisure time for active pursuits, including exercise, may be contingent upon jobs which promote interaction, learning, and activity on the job. In investigating whether the psychosocial structure of work might affect smoking and sedentary behavior, a subsample (n = 7.201) of a representative sample of the Swedish population aged 16-65 years was selected for study. Reports on job characteristics and health behaviors were obtained in personal or telephone interviews and a logistic regression analysis was performed. In general, job demands like shift work, piece work, hazardous exposure, and physical load tended to be associated with smoking and sedentary behavior, whereas job resources, including personal autonomy, were predictive of regular exercise, but unrelated to smoking behavior. Correlational patterns varied somewhat between sexes. The implications of these findings with respect to work organization, considerations in epidemiological research, and the conduct of health promotion programs are discussed.

Health Behavior↗

PubMed2025

Causal relationships between modifiable risk factors and heart failure: A comprehensive Mendelian randomization study.

Heart failure threatens human health across the globe. Comprehensively identifying its risk factors has public health importance. This work utilized the Mendelian randomization (MR) method to evaluate the effects of over 200 modifiable factors on heart failure. The data from genome-wide association studies (GWAS) was used, with the sample size ranging from 711 to 1232,091. Two distinct GWAS datasets for heart failure were employed for results validation. The inverse variance weighted (IVW) method was used and other supplementary models were employed for comparison. Sensitivity analysis was conducted to verify the results. After integrating the MR estimates derived from heart failure GWAS datasets from integrative epidemiology unit (IEU) and Finngen, we found that body measurement indices like body mass index, whole body fat mass, trunk fat mass, basal metabolic rate, body fat percentage, waist circumference, and waist-hip ratio, were associated with a higher risk of heart failure. Similarly, smoking behavior, sedentary behavior, overall health rating, and type 2 diabetes were determined to increase the risk of heart failure. In contrast, college or university degree showed a protective effect on heart failure. Among these significant findings, body mass index, whole body fat mass, trunk fat mass, basal metabolic rate, body fat percentage, overall health rating, smoking initiation, waist circumference, lifetime smoking index, college or university degree, sedentary behavior, waist-hip ratio, and type 2 diabetes were replicated validated. This MR work figured out that obesity, socioeconomic factors, lifestyle factors, and metabolic features showed broad relations with heart failure. The findings would provide evidence for future policy development for the management of heart failure.

Humans↗

PubMed2026

Causal relationships between somatic movement, brain structures, and mental well-being: A multi-stage Mendelian randomization study.

BACKGROUND: While the relationships between somatic movement, mental well-being, and brain health have been well established, the causal nature and underlying mechanisms of such associations remain incompletely understood. METHODS: By applying multi-stage Mendelian randomization to multi-source summary data derived from genome-wide association studies, we examined the causal effects of 4 somatic movement measures on 2 mental well-being indices and 13 types of brain structures, followed by testing the mediating roles of brain structures in accounting for the causal associations between somatic movement and mental well-being. RESULTS: Two-sample Mendelian randomization revealed that more physical activity was causally associated with greater mental well-being (life satisfaction and positive affect), while more sedentary behavior (longer leisure screen time and more sedentary behavior at work) with lower mental well-being. With respect to brain structures, sedentary behavior was causally linked to decreased volume, surface area, and local gyrification index in distributed cortical regions. Remarkably, decreased surface area of the piriform cortex was found to mediate the causal associations between sedentary behavior and lower mental well-being. CONCLUSIONS: Our findings not only complement and extend earlier reports on the associations of somatic movement with mental well-being and brain health by further resolving the causality but also help elucidate the neural mechanisms by which sedentary behavior adversely affects mental well-being.

Humans↗

PubMed2025

Exploring the causal association between television viewing and meniscal injuries: A two-sample Mendelian randomization analysis.

The aim of this study was to assess whether there is a potential causal relationship between sedentary behavior and meniscal injuries based on the Mendelian randomization (MR) method. This study used a two-sample MR design to integrate pooled data from a large-scale genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) that were significantly associated with sedentary behavior (represented by daily TV-viewing time) and independent of each other were selected as instrumental variables, while focusing on data from populations of European ancestry. To ensure the robustness and reliability of the analyses, 3 mainstream MR analysis methods were combined in this study: inverse variance weighted (IVW), weighted median estimation (WME) and MR-Egger regression. Heterogeneity test, horizontal multivariate analysis, and leave-one-out sensitivity test were also conducted to further validate the stability of causal estimation. The results of the IVW method showed that sedentary behavior was significantly associated with the risk of meniscus injury, with an OR (95% CI) of 2.93 (1.89-4.52), and a P-value of < .001, suggesting that sedentary behavior may be an important risk factor for meniscus injury. No significant bias was found in the heterogeneity test and the assessment of multiple validity, and the sensitivity analysis showed that the effect of individual SNPs on the overall estimation was small, and the results had good robustness. This study provides genetic epidemiological evidence of a positive causal effect of sedentary behavior on meniscal injuries based on a causal inference approach with genetic instrumental variables. The results suggest that reducing sedentary time, especially prolonged TV watching behavior, may reduce the risk of meniscus injury to some extent.

Humans↗

PubMed2026

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n = 64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with lower insulin sensitivity (r=-0.35, p = 0.005), higher resting O2 consumption (r = 0.41, p < 0.001), higher resting energy expenditure (r = 0.49, p < 0.001), higher LFC (r = 0.40, p = 0.011), and greater left ventricular wall thickness (r = 0.42, p = 0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r = 0.29, p = 0.032), improved insulin sensitivity (r = -0.26, p = 0.045), and increased cardiorespiratory fitness (r = -0.29, p = 0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify the role of Hb levels in this high-risk group.

Humans↗

PubMed2024

Leisure television watching exerts a causal effect on gastroesophageal reflux disease: evidence from a two-step mendelian randomization study.

BACKGROUND: Previous studies have shown that physical activity (PA) and leisure sedentary behaviors (LSB, including leisure television watching) are linked to gastroesophageal reflux disease (GERD). However, the associations between PA/LSB and GERD remain controversial. In this study, we aimed to reveal whether these associations reflect causal relationships and reveal the potential mechanisms of these relationships using bidirectional and two-step Mendelian randomization (MR) analyses. METHODS: We obtained genome-wide association study (GWAS) summary statistics for PA/LSB, four common risk factors (including cigarettes smoked per day, alcoholic drinks per week, triglycerides, total cholesterol) and GERD from published GWASs. A bidirectional MR analysis was performed to identify causal relationships between PA/LSB and GERD. Then, a series of sensitivity analyses were performed to verify the robustness of the results. Finally, a mediation analysis via two-step MR was conducted to investigate any effects explained by common risk factors in these relationships. RESULTS: Genetically predicted per 1-SD increase in leisure time television watching significantly increased the risk of GERD in the bidirectional MR analysis (OR = 1.33; 95% CI: 1.14-1.56; P = 2.71 × 10- 4). Sensitivity analyses successfully verified the robustness of the causal relationship. Further mediation analysis showed that this effect was partly mediated by increasing cigarettes smoked per day, with mediated proportions of 18.37% (95% CI: 11.94-39.79%). CONCLUSION: Our findings revealed a causal relationship between leisure television watching and an increased risk of GERD, notably, the causal effect was partially mediated by cigarettes smoked per day. These findings may inform prevention and management strategies directed toward GERD.

Humans↗

PubMed2026

Plasma Proteomic Signatures of Physical Activity Provide Insights into Biological Impacts and its Protective Role against Dementia.

PURPOSE: Physical activity (PA) and sedentary behavior (SB) are associated with many diseases, including Alzheimer disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. This study aims to address this gap, with a specific focus on all-cause dementia. METHODS: We first assessed the conventional observational associations of three self-reported and three device-based PA/SB measures with circulating levels of 2911 plasma proteins measured in the UK Biobank ( nmax = 39,160) and assessed functional enrichment of identified proteins. We then used bidirectional Mendelian randomization to further evaluate the evidence for causal relationships of PA/SB with protein levels. Finally, we performed mediation analyses to identify proteins that may mediate the relationship of PA with incident all-cause dementia. RESULTS: Our findings revealed 41 proteins consistently associated with all PA measures and 1027 proteins associated with at least one PA measure. Both conventional observational and Mendelian randomization study designs converged on proteins that appear to increase as a result of PA, including integrins such as ITGAV and ITGAM, as well as MXRA8, CLEC4A, CLEC4M, LPL, and ADGRG2; and on proteins that appear to decrease as a result of PA such as LEP, INHBC, CLMP, PTGDS, ADM, OGN, and PI3; and on proteins that are more responsive to high-intensity PA, such as CA14, CA6, CA4, KIT, and ANGPT2. Functional enrichment analyses revealed processes such as cell-matrix adhesion, integrin-mediated signaling, and collagen binding. Finally, GDF15, ITGAV, ITGAM, ITGA11, HPGDS, GFAP, ADM, AHNAK, and DPP4 were among 21 unique proteins found to mediate the relationship of PA with all-cause dementia, implicating processes such as synaptic plasticity, neurogenesis, and inflammation. CONCLUSIONS: Our results provide insights into how PA affects biological processes and protects against dementia, and provide avenues for future research into the health-promoting effects of PA.

Humans↗

PubMed1991

Physical activity and hypertension in black adults: the Pitt County Study.

The relation of physical activity to hypertension was examined in 1751 Black adults in Pitt County, NC. More women (65%) than men (44%) were classified as sedentary. Sedentary behavior was not associated with the prevalence of hypertension in men, but was associated with a 31% increase in prevalence for women (sedentary-26.2%; active-20.0%; P less than .01). The association in women was independent of other risk factors for hypertension.

Adult↗

PubMed2026

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans↗

PubMed1992

Distribution and correlates of waist-to-hip ratio in black adults: the Pitt County Study.

A 1988 community-based survey of 1,784 black adults aged 25-50 years in Pitt County, North Carolina, found mean waist-to-hip ratios of 0.890 for men and 0.852 for women. Based on guidelines from the US Department of Agriculture, 20% of the men and 76% of the women had an elevated waist-to-hip ratio. Sedentary behavior was associated with elevated waist-to-hip ratio in men, while a similar excess was associated with alcohol consumption in women. Weak, nonsignificant associations with waist-to-hip ratio were observed for smoking. Socioeconomic status was unrelated to waist-to-hip ratio in men, but it had a strong inverse relation for women.

Adipose Tissue↗

PubMed2026

Effects of short-bout accumulated exercise on postprandial metabolism in adults: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the acute effects of short-bout accumulated exercise (SBAE) interrupting prolonged sedentary behaviour on postprandial glucose, insulin, and triglycerides in adults. METHODS: Systematic searches in PubMed, Web of Science, Embase, Cochrane Library, CINAHL, SPORTDiscus, and CNKI (inception to 10 December 2025) identified randomised crossover trials comparing SBAE (≤10 min/bout, inter-bout interval ≥30 min or adequate recovery) with continuous sedentary behaviour. Outcomes included postprandial glucose, insulin, and triglyceride AUCs. Standardised mean differences (SMD) were pooled using random-effects models. RESULTS: Thirty-one publications reporting data from 29 independent cohorts involving 573 unique participants (mean age 47.8 ± 20.3 years; 47.5% female; mean BMI 29.0 ± 5.1 kg/m²) were included. Compared with continuous sedentary behaviour, SBAE significantly reduced glucose AUC (SMD = -0.53, 95% CI: -0.71 to -0.34, P < 0.001) and insulin AUC (SMD = -0.58, 95% CI: -0.85 to -0.31, P < 0.001), but not triglyceride AUC (SMD = -0.17, 95% CI: -0.48 to 0.15, P = 0.306).Exploratory subgroup analyses showed statistically significant reductions in glucose and insulin for walking and for inter-bout intervals < 60 min, but not for standing alone or intervals ≥ 60 min. A statistically significant insulin-lowering effect was observed in obese individuals. CONCLUSION: SBAE acutely improves postprandial glucose and insulin control. Exploratory subgroup analyses showed statistically significant effects for walking and for inter-bout intervals < 60 min, but these comparisons are observational and no formal interaction test was conducted. These findings provide preliminary evidence for acute SBAE in sedentary populations, though long-term health effects and real-world generalisability require further investigation.

Adult↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗

PubMed1992

The role of efficacy cognitions in the prediction of exercise behavior in middle-aged adults.

The present study adopted a social cognitive framework to examine the role played by perceptions of personal efficacy in adherence to exercise behavior in sedentary middle-aged adults. Subjects were followed for 5 months in order to study the process of exercise as it moved through the adoption to maintenance stage of the behavior. Participation rates paralleled those reported elsewhere in the literature. Path analytic techniques examined the role over time of efficacy, perceptual, and behavioral indicators of frequency and intensity of exercise. Self-efficacy cognitions were shown to predict adoption of exercise behavior but previous behavior proved to be the strongest predictor of subsequent exercise participation. Results are discussed in terms of examining process versus static design models in exercise and physical activity research. Implications for future research and health promotion are suggested.

Aging↗

PubMed2026

Joint association of sedentary behaviour and physical activity with cardiovascular disease: a systematic review and meta-analysis.

This systematic review and meta-analysis of cohort studies aimed to synthesize existing evidence on the joint association of physical activity (PA) and sedentary behaviour (SB) with cardiovascular disease (CVD) risk among adults. We searched PubMed, EMBASE, and Cochrane for English studies published between January 2010 and February 2025 that examined the joint association of PA and SB (fatal and non-fatal) CVD among adults and pooled their results through meta-analyses using study-level data. Using findings from 17 studies, the pooled effect size for the lowest PA + highest SB group was 1.78 (95% CI: 1.59-2.00), suggesting increased risk for CVD compared with the reference group (i.e. highest PA + lowest SB). Compared with the same reference group, we found an increased risk for CVD in the lowest PA + lowest SB (HR = 1.25, 95% CI: 1.12-1.40) and the highest PA + highest SB (HR = 1.16, 95% CI: 1.06-1.27) groups. Subgroup analyses according to domains or types of PA and SB exposure, outcome measures, and exposure measurement method revealed a similar pattern. In conclusion, individuals with the lowest PA combined with the highest SB may experience an increased risk for CVD events compared with those with the highest PA and lowest SB. There was also an increased risk for individuals with a combination of either low PA + low SB and high PA + high SB, albeit to a lesser extent. Although substantial study-level heterogeneity exists, the results highlight the potential value of considering both behaviours jointly in relation to CVD risk.

Humans↗

PubMed2024

Causal effects of sedentary behaviours on the risk of migraine: A univariable and multivariable Mendelian randomization study.

BACKGROUND: Migraine is a common and burdensome neurological disorder. The causal relationship between sedentary behaviours (SBs) and migraine remains instinct. We aimed to evaluate the roles of SBs including watching TV, using computer and driving in the risk of migraine. METHODS: We conducted a univariable and multivariable Mendelian randomization (MR) study based on summary datasets of large genome-wide association studies. The inverse variance weighted method was utilized as the primary analytical tool. Cochran's Q, MR-Egger intercept test, MR pleiotropy residual sum and outlier and leave-one-out were conducted as sensitivity analysis. Additionally, we performed a meta-analysis to combine the causal estimates. RESULTS: In the discovery analysis, we identified causal associations between time spent watching TV and an increased risk of migraine (p = 0.015) and migraine without aura (MO) (p = 0.002). Such causalities with increasing risk of migraine (p = 0.005), and MO (p = 0.006) were further verified using summary datasets from another study in the replication analysis. There was no significant causal association found between time spent using computer, driving and migraine or its two subtypes. The meta-analysis and multivariable MR analysis also strongly supported the causal relationships between time spent watching TV and an increased risk of migraine (p = 0.0003 and p = 0.034), as well as MO (p < 0.0001 and p = 0.0004), respectively. These findings were robust under all sensitivity analysis. CONCLUSIONS: Our study suggested that time spent watching TV may be causally associated with an increased risk of migraine, particularly MO. Large-scale and well-designed cohort studies may be warranted for further validation. SIGNIFICANCE STATEMENT: This study represents the first attempt to investigate whether a causal relationship exists between SBs and migraine. Utilizing MR analysis helps mitigate reverse causation bias and confounding factors commonly encountered in observational cohorts, thereby enhancing the robustness of derived causal associations. Our MR analysis revealed that time spent watching TV may serve as a potential risk factor for migraine, particularly MO.

Humans↗