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The Associations between Modifiable Factors and Irritable Bowel Syndrome: Evidence from Genetic Correlation and Mendelian Randomization Study
33 Pages Posted: 25 Apr 2024
More...Abstract
Background: It is of high priority to identify potentially modifiable factors, to help develop targeted prevention strategies for irritable bowel syndrome (IBS). Our study aimed to systematically explore the causal associations between modifiable factors and IBS.
Methods: Genetic evidence from genetic correlation and Mendelian randomization (MR) approach were performed using summary GWAS data to assess causal associations of factors with IBS. Genome-wide linkage disequilibrium score regression (LDSC) was first used to explore the genetic correlation, then univariable and multivariable MR (MVMR) method were used to calculate MR estimates of associations between factors and IBS.
Findings: Extensive genetic correlations and genetic overlaps showed more than half of the modifiable factors associated with IBS. MR analyses further showed genetically predicted alcohol frequency (OR=1.13, 95%CI=1.04-1.24), well-being spectrum related neuroticism score (OR=1.14, 95%CI=1.06-1.22), insomnia (OR=1.71, 95%CI=1.43-2.05), schizophrenia (OR=1.04, 95%CI=1.01-1.07), externalizing traits (OR=1.35, 95%CI=1.19-1.52), obesity (OR=1.13, 95%CI=1.03-1.24), waist circumference (OR=1.09, 95%CI=1.02-1.16), triglycerides (OR=1.10, 95%CI=1.05-1.14), frailty index (OR=1.64, 95%CI=1.22-2.21), haemorrhoidal disease (OR=1.08, 95%CI=1.00-1.15), and gastroesophageal reflux disease (OR=1.41, 95%CI=1.25-1.60) were associated with the increased risk of IBS, while higher education (OR=0.55, 95%CI=0.39-0.73) and well-being spectrum (OR=0.30, 95%CI=0.17-0.51) and related life satisfaction (OR=0.45, 95%CI=0.28-0.75) and positive affect (OR=0.41, 95%CI=0.26-0.66) were associated with the decreased risk of IBS. MVMR analyses confirmed the associations of gastroesophageal reflux disease, well-being spectrum and related traits, waist circumference, frailty index with IBS.
Interpretation: Our findings suggest an extensive series of potential protective or risk factors for the occurrence of IBS. Further studies are needed to assess these modifiable factors for primary prevention of IBS.
Funding: China Postdoctoral Science Foundation (grant number 2021M703366), the Shenzhen Science and Technology Program (Grant No. KQTD20190929172835662) and the Strategic Priority Research Program of Chinese Academy of Sciences (grant no. XDB 38040200).
Declaration of Interest: The authors declare that they have no competing interests.
Ethical Approval: All the GWASs included had been approved by corresponding institutional review boards and ethical committees. All participants had signed informed consent.
Keywords: irritable bowel syndrome, modifiable factors, genetic correlation, Mendelian randomization, primary prevention
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