Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study

Abstract

Background and Aims:The risk factors of cholelithiasis have not been clearly identified, especially for total cholesterol. Here, we try to identify these causal risk factors. Approach and Results:We obtained genetic variants associated with the exposures at the genome-wide significance (p < 5 × 10 −8 ) level from corresponding genome-wide association studies. Summary-level statistical data for cholelithiasis were obtained from FinnGen and UK Biobank (UKB) consortia. Both univariable and multivariable Mendelian randomization (MR) analyses were conducted to identify causal risk factors of cholelithiasis. Results from FinnGen and UKB were combined using the fixed-effect model. In FinnGen, the odds of cholelithiasis increased per 1-SD increase of body mass index (BMI) (OR = 1.631, p = 2.16 × 10 −7 ), together with body fat percentage (OR = 2.108, p = 4.56 × 10 −3 ) and fasting insulin (OR = 2.340, p = 9.09 × 10 −3 ). The odds of cholelithiasis would also increase with lowering of total cholesterol (OR = 0.789, p = 8.34 × 10 −5 ) and low-density lipoproteincholesterol (LDL-C) (OR = 0.792, p = 2.45 × 10 −4 ). However, LDL-C was not significant in multivariable MR. In UKB, the results of BMI, body fat percentage, total cholesterol, and LDL-C were replicated. In meta-analysis, the liability to type 2 diabetes mellitus and smoking could also increase the risk of cholelithiasis. Moreover, there were no associations with other predominant risk factors.Conclusions: Our MR study corroborated the risk factors of cholelithiasis from previous MR studies. Furthermore, lower total cholesterol level could be an independent risk factor.

Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study

“…Finally, we assessed the power of remaining SNPs using the F statistics (F = beta 2 /se 2 ) for each SNP. SNPs with less statistical power would be removed to avoid weak instrumental variables (F statistics <10) ( Chen L. et al, 2021 ).…”

Alleviating insomnia should decrease the risk of irritable bowel syndrome: Evidence from Mendelian randomization

“…The number of IVs for each exposure varied from 12 (long sleep duration) to 196 (chronotype). The F statistic for each SNP was greater than the empirical threshold of 10 ( Chen et al, 2022 ) and the overall F statistic for each exposure was larger than 10 as well, suggesting the results were less likely to be biased by the weak instruments. The MR Steiger test indicated that each IV explained more variance in exposure than that of the outcome, meaning the results might not be biased by the reverse causation.…”

Construction and Evaluation of a Nomogram to Predict Gallstone Disease Based on Body Composition

“…Cholelithiasis (gallstone disease) affects approximately 10%~20% of adults globally and is among the hepatobiliary diseases associated with the highest socioeconomic costs. 17 , 18 In addition, cholelithiasis is also an important risk factor for gallbladder cancer, and it is increasingly recognized as a public health concern that needs more attention. 17 , 19 Although epidemiological studies have identified risk factors associated with cholelithiasis, primary prevention remains weak.…”

“… 17 , 18 In addition, cholelithiasis is also an important risk factor for gallbladder cancer, and it is increasingly recognized as a public health concern that needs more attention. 17 , 19 Although epidemiological studies have identified risk factors associated with cholelithiasis, primary prevention remains weak. 3 We found that there are few individual-based risk prediction models for cholelithiasis.…”