The relationship between inflammatory bowel disease and sarcopenia-related traits: a bidirectional two-sample mendelian randomization study.

Observational studies have revealed a link between inflammatory bowel disease (IBD) and sarcopenia. However, it remains unclear whether this correlation between IBD and sarcopenia is causal. The genetic instrumental variables (IVs) associated with IBD and sarcopenia-related traits were derived from publicly available genome-wide association studies. We employed a two-sample bidirectional Mendelian randomization (MR) method. we obtained genetic IVs for five phenotypes from 34,652 cases in IBD, 27,432 cases in ulcerative colitis (UC), 212356 cases in crohn's disease (CD), 9336415 cases in low hand grip strength (LHGS), and 450243 cases in appendicular lean mass (ALM), respectively. The inverse variance weighting and other MR methods were used to explore the bidirectional causal relationship. Furthermore, we performed heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate MR to evaluate the robustness of the results. The forward MR results showed that the UC (OR=0.994, 95% CI: 0.9876-0.9998, P = 0.044) and CD (OR=0.993, 95% CI: 0.988-0.998, P = 0.006) was negatively correlated with ALM. In the reverse MR analysis, we also found that LHGS was negatively correlated with the IBD (OR=0.76, 95% CI: 0.61-0.94, P = 0.012) and CD (OR=0.53, 95% CI: 0.40-0.70, P <0.001). Besides, genetically predicted higher ALM reduced IBD (OR=0.87, 95% CI: 0.79-0.95, P = 0.002), UC (OR=0.84, 95% CI: 0.76-0.93, P = 0.001), and CD (OR=0.87, 95% CI: 0.77-0.99, P = 0.029). However, the results of other MR Analyses were not statistically different. We found genetically predicted UC and CD are causally associated with reduced ALM, and higher hand grip strength reduced IBD and CD risk, and higher ALM reduced IBDs risk. This MR study provides moderate evidence for a bidirectional causal relationship between IBD and sarcopenia.

Sun Z ，Liu G ，Xu J ，Zhang X ，Wei H ，Wu G ，Jiang J ... -  《Frontiers in Endocrinology》

Exploring the causal relationship between inflammatory bowel disease and sarcopenia-related traits: a two-sample Mendelian randomization analysis.

Lin S ，Zhang C ，Chen C ，Fan Y ，Yang F ... -  《Aging-US》

A bidirectional Mendelian randomization study of sarcopenia-related traits and inflammatory bowel diseases.

There is increasing evidence pointing to a close relationship between sarcopenia and inflammatory bowel disease. However, it remains unclear whether or in which direction causal relationships exist, because these associations could be confounded. We conducted a two-sample bidirectional mendelian randomization analysis using data from European genome-wide association studies of the appendicular lean mass(n = 450,243), walking pace(n = 459,915), grip strength (left hand, n = 461,026; right hand, n = 461,089), inflammatory bowel disease (25,042 patients and 34,915 controls), ulcerative colitis (12,366 patients and 33,609 controls), and Crohn's disease (12,194 patients and 28,072 controls) to investigate the causal relationship between sarcopenia-related traits and inflammatory bowel disease and its subtypes on each other. The inverse-variance weighted method was used as the primary analysis method to assess the causality, and a comprehensive sensitivity test was conducted. Genetically predicted appendicular lean mass was significantly associated with inflammatory bowel disease (OR = 0.916, 95%CI: 0.853-0.984, P = 0.017), ulcerative colitis (OR =0.888, 95%CI: 0.813-0.971, P = 0.009), and Crohn's disease (OR = 0.905, 95%CI: 0.820-0.999, P = 0.049). Similar results also revealed that the usual walking pace was causally associated with Crohn's disease (OR = 0.467, 95%CI: 0.239-0.914, P = 0.026). Reverse mendelian randomization analysis results found that genetic susceptibility to inflammatory bowel disease, and Crohn's disease were associated with lower appendicular lean mass. A series of sensitivity analyses ensured the reliability of the present research results. The mendelian randomization study supports a bidirectional causality between inflammatory bowel disease, Crohn's disease and appendicular lean mass, but no such bidirectional causal relationship was found in ulcerative colitis. In addition, genetically predicted usual walking pace may reduce the risk of Crohn's disease. These findings have clinical implications for sarcopenia and inflammatory bowel disease management.

Jiao X ，Wu WY ，Zhan SF ，Liu JB ，Zhang XJ ... -  《Frontiers in Immunology》

Causal Association Analysis of Periodontitis and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

Periodontitis has been reported to be associated with inflammatory bowel disease (IBD), including ulcerative colitis (UC), and Crohn's disease (CD). However, the causality of these 2 diseases remains unclear. We conducted bidirectional Mendelian randomization (MR) to investigate the causal relationship between periodontitis and IBD. We obtained the genome-wide association study (GWAS) summary data of European populations from FinnGen database (for IBD) and a published article (for periodontitis), from which independent single nucleotide polymorphisms were selected as instrumental variables. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for MR analysis. Heterogeneity or pleiotropy was detected through Cochran's Q test and MR-Egger intercept, respectively. Outlier was identified with MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) and leave-one-out analysis. All statistical analyses were performed with R 4.2.1 and the packages of TwoSampleMR version 0.5.6. Genetic prediction showed that periodontitis was the risk factor of UC (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.26; P = .027), rather than of CD (OR, 0.92; 95% CI, 0.74-1.15; P = .456) and IBD (OR, 0.96; 95% CI, 0.81-1.13; P = .619). To the contrary, CD, not UC or IBD, resulted in exacerbating periodontitis in terms of the results of the IVW (OR, 1.09; 95% CI, 1.01-1.17; P = .021) and WM (OR, 1.10; 95% CI, 1.01-1.20; P = .030) methods. Heterogeneity or pleiotropy was acceptable. Our results indicated that CD was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of UC, enhancing the existence of mouth-gut axis. Patients with UC should pay more attention to periodontal health, while patients with periodontitis should actively pay close heed to intestinal health.

Qing X ，Zhang C ，Zhong Z ，Zhang T ，Wang L ，Fang S ，Jiang T ，Luo X ，Yang Y ，Song G ，Wei W ... -  《-》

Assessment of the causal relationship between inflammatory bowel diseases and chronic kidney diseases: A two-sample bidirectional mendelian randomization study among European population.

Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear. We determined the causal association between IBD and CKD by performing two-sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open-access genome-wide association studies (GWAS) among European ancestry. IVs-outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse-variance-weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta-analysed. Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016-1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027-1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969-1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965-1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948-1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963-1.089, p = 0.447). We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD.

Li X ，Ge Q ，Yu C ，Zhao W ，Wu C ，Liu Z ，Meng X ，Xiao C ... -  《-》