In a recent study published in the Scientific Reports journal, researchers employed Mendelian randomization analyses of large-scale genome-wide association studies to investigate the causal relationship between leisure screen time (LST) and irritable bowel syndrome (IBS).
Their results establish the association between increased leisure screen time and irregular bowel movements in Europeans, paving the path for future investigations into the biological mechanisms underlying computed correlations.
Study: The causal effects of leisure screen time on irritable bowel syndrome risk from a Mendelian randomization study. Image Credit: OPOLJA/Shutterstock.com
The dangers of LST and IBS
Irritable bowel syndrome (IBS) is a chronic condition affecting the gastrointestinal tract (GI). It is characterized by abdominal cramping, pain, bloating, diarrhea or constipation, or both. The altered bowel patterns associated with the condition are common, affecting 10-20% of the world’s population, with an additional incidence of 1-2% per year.
The pathology and etiology of the disease are multifaceted, with genetics, infection, intestinal motility, and chronic inflammation assumed to contribute to IBS.
The severity of IBS varies between individuals, with coexisting conditions including poor lifestyle and health behaviors and emotional or mental stress amplifying disease symptoms. There is currently no unambiguously effective treatment for the condition, making studying the causal underpinnings of the disease essential.
A growing body of literature identifies extended sedentary behaviors, especially leisure screen time (LST), contributing to chronic illnesses like diabetes, cardiovascular disease (CVD), and cancer. However, few studies have investigated the associations between LST and IBS risk.
A sedentary lifestyle has increased the risk of non-communicable diseases, especially cancers, mental health issues, and CVD.
Large cohort observational studies and meta-analyses have revealed that excess LST, one of the most detrimental sedentary behaviors, is independently responsible for CVD and cancers of the lung, breast, colon, and prostate. Alarmingly, every additional two hours of television watching has been reported to increase colorectal cancer risk by 1.07%.
The relationship between physical activity levels and IBS is scant and confounding. While some cross-sectional studies have shown that physical inactivity is independently responsible for IBS, others have reported increased physical activity resulting in increased abdominal IBS symptoms.
While the biological mechanisms surrounding LST and IBS remain elusive, situational evidence points to exercise training lowering IBS risk due to improved intestinal transit and the body’s ability to cope with emotional stress.
Most of this research remains observational, making an unbiased establishment of the links between lower physical activity and IBS risk imperative.
About the study
The present study employed Mendelian Randomization (MR) approaches to investigate LST and IBS risk associations. Mendelian randomization is a form of instrumental variable (IV) analysis that uses single nucleotide polymorphism (SNP) associations from genome-wide association studies (GWAS) as instruments to study and uncover causal relationships between complex traits.
These studies are unaffected by confounding variables that bias most observational studies. For an IV to be valid in an MR study, it must satisfy three main assumptions.
“(1) the SNPs are strongly associated with the exposure (leisure screen time); (2) Each SNP is independent of confounding variables; and (3) There is only one possible mechanism by which each SNP is related with the outcome, and that is through the exposure”.
The present study used summary statistics and GWAS meta-data from the UK Biobank and FinnGen consortium, representing 58,005 cases of IBS and 615,624 normal controls.
The dataset comprised 19.1–22.5 million SNPs per trait, with individual-recorded variables including sex, ancestry, and type of sedentary LST activity (watching television versus using the computer).
Exposure duration was measured via a questionnaire recording time spent using the TV or computer for non-work leisure or recreational activities. Only individuals of European descent were included in the statistical analysis to minimize ethnicity bias.
Effect allele frequencies (EAFs) were used to identify SNPs associated with IBS risk, and F-statistics calculated the exposure strength and eliminated weak instrument biases from the two datasets.
Pleiotropy, the effects of a single gene (or, in this case, SNP) to affect two or more phenotypic traits, was computed using an MR-Egger regression method.
Confounding characteristics, including body fat mass, adiposity, body mass index (BMI), body fat percentage, and waist-to-hip ratio, were removed before rerunning the MR analysis to evaluate the impacts of these variables on IBS association or strength.
Finally, Cochrane’s Q value was used to estimate heterogeneity in the association between LST and IBS.
Results identified 94 significant SNPs linked with LST. Of these, 61 SNPs were found to be possible independent IVs related to LST. The MR-Egger regression model did not reveal any IVs associated with horizontal pleiotropy, eliminating biases obtained from a single IV having multiple LST associations.
Before confounding variables were removed, Cochrane’s Q value computations identified high heterogeneity in the association between LST and IBS.
Previous studies have reported that adiposity and BMI are correlated with LST, with the former potentially mediating the causation or symptom strength of the latter. This would result in confounding effects, so SNPs associated with BMI were removed, resulting in 47 remaining SNPs.
Cochrane’s Q value computations for these SNPs found negligible heterogeneity, which revealed that all 47 SNPs linked LST with an increased risk of IBS.
Results from the FinnGen consortium dataset, while having only borderline statistical significance (p = 0.054), mirrored and strengthened the statistical foundations of the UK Biobank dataset (p = 0.004).
In the present study, researchers employed Mendelian randomization analyses in data mining a two-study GWAS dataset to elucidate the causative role of LST in increasing IBS risks.
Results from their final dataset comprising 58,005 cases of IBS and 615,624 normal controls revealed 94 SNPs linked to LST. After confounding SNPs were removed, the analyses revealed 47 SNPs establishing the causative function of LST in escalating the risk of IBS contraction.
This study thus represents the first concrete and non-observational evidence linking LST and other sedentary behaviors to IBS. It forms the basis for future studies investigating the biological and pathomechanistic associations between behavior and the condition.
A growing body of literature shows that physical activity today is much lower than a decade ago, making studies into the adverse casual functions of sedentary lifestyle choices both relevant and essential.