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Physical activity and risk of gallstone disease: A Mendelian randomization study.

ABSTRACT: Objective: Given the association between physical activity and the reduced risk of gallstone disease as suggested in observational studies, a Mendelian randomization study was conducted to evaluate the causal nature of this association in genetic epidemiology. Study: Including self-reported and accelerometer-based physical activity traits, the independent genetic variants associated with physical activity were selected from the corresponding genome-wide association studies as instrumental variables. The summary-level data for gallstone disease were sourced from the UK Biobank (7,682 cases and 455,251 non-cases) and FinnGen consortium (23,089 cases and 231,644 non-cases). Then, two-sample Mendelian randomization analysis was conducted. Inverse-variance weight (IVW), weighted median, and Mendelian randomization-Egger regression were determined through Mendelian randomization analyses. To ensure the robustness of the results, sensitivity analyses were also carried out in the study. Results: The negative causality between the genetically predicted accelerometer-based "average acceleration" physical activity and the risk of gallstone disease was suggested in the UK Biobank study (p = 0.023, OR = 0.93, 95% CI: 0.87-0.99), and accelerometer-based "overall activity" physical activity and the risk of gallstone disease in the UK Biobank study (p = 0.017, OR = 0.38, 95% CI: 0.17-0.84). With accelerometer-based "average acceleration" physical activity negatively correlated with gallstone disease in the FinnGen consortium data (p = 0.001, OR = 0.94, 95% CI: 0.90-0.97). As for self-reported moderate-to-vigorous physical activity, however, there was no causality observed in both pieces of data. Conclusion: Our studies provide the evidence suggesting a casual association between physical activities and gallstone disease through analysis of genetic data. As indicated by the research results, there is a possibility that a higher level of physical activities could mitigate the risk of gallstone disease.

SUBMITTER: Qian Q

PROVIDER: S-EPMC9763559 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Physical activity and risk of gallstone disease: A Mendelian randomization study.

Qian Qilin Q Jiang Han H Cai Bingyue B Chen Dingwan D Jiang Minmin M

Frontiers in genetics 20221206

<b>Objective:</b> Given the association between physical activity and the reduced risk of gallstone disease as suggested in observational studies, a Mendelian randomization study was conducted to evaluate the causal nature of this association in genetic epidemiology. <b>Study:</b> Including self-reported and accelerometer-based physical activity traits, the independent genetic variants associated with physical activity were selected from the corresponding genome-wide association studies as instr ...[more]

PMID: 36561321

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Project description:Pancreatic cancer is currently the seventh leading cause of cancer death worldwide. Understanding whether modifiable factors increase or decrease the risk of this disease is central to facilitating primary prevention. Several epidemiological studies have described the benefits of physical activity, and the risks associated with sedentary behavior, in relation to cancer. This study aimed to assess evidence of causal effects of physical activity and sedentary behavior on pancreatic cancer risk. We conducted a two-sample Mendelian randomization study using publicly available data for genetic variants associated with physical activity and sedentary behavior traits and genetic data from the Pancreatic Cancer Cohort Consortium (PanScan), the Pancreatic Cancer Case-Control Consortium (PanC4), and the FinnGen study for a total of 10 018 pancreatic cancer cases and 266 638 controls. We also investigated the role of body mass index (BMI) as a possible mediator between physical activity and sedentary traits and risk of developing pancreatic cancer. We found evidence of a causal association between genetically determined hours spent watching television (hours per day) and increased risk of pancreatic cancer for each hour increment (PanScan-PanC4 odds ratio = 1.52, 95% confidence interval 1.17-1.98, P = .002). Additionally, mediation analysis showed that genetically determined television-watching time was strongly associated with BMI, and the estimated proportion of the effect of television-watching time on pancreatic cancer risk mediated by BMI was 54%. This study reports the first Mendelian randomization-based evidence of a causal association between a measure of sedentary behavior (television-watching time) and risk of pancreatic cancer and that this is strongly mediated by BMI. Summary: Pancreatic cancer is a deadly disease that is predicted to become the second leading cause of cancer-related deaths by 2030. Physical activity and sedentary behaviors have been linked to cancer risk and survival. However, there is limited research on their correlation with pancreatic cancer. To investigate this, we used a Mendelian randomization approach to examine the genetic predisposition to physical activity and sedentariness and their relation to pancreatic cancer risk, while excluding external confounders. Our findings revealed a causal link between the time spent watching television and an increased risk of pancreatic cancer. Additionally, we determined that over half of the effect of watching television on pancreatic risk is mediated by the individual's BMI.

Dataset Information

Physical activity and risk of gallstone disease: A Mendelian randomization study.

Publications

Physical activity and risk of gallstone disease: A Mendelian randomization study.

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