Background: Associations between inflammatory bowel disease (IBD) [including ulcerative colitis (UC) and Crohn's disease (CD)] and ankylosing spondylitis (AS) were discovered in observational studies, but no evidence supported the causal relationship between the two diseases. Methods: We employed two-sample Mendelian randomization (MR) to estimate the unconfounded bidirectional causal associations between IBD (including UC and CD) and AS. We selected single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) after strictly assessing the quality of the studies in the IEU GWAS database. Sensitivity analyses were also conducted to verify whether heterogeneity and pleiotropy can bias the MR results. Results: We found positive causal effects of genetically increased UC, CD, and IBD risk on AS (e.g., UC and AS, IVW OR: 1.0256, 95% CI: 1.0130∼1.0385, p = 6.43E-05). However, we did not find significant causal associations of AS with UC, CD, or IBD (e.g., AS and UC, IVW OR: 1.1858, 95% CI: 0.8639∼1.6278, p = 0.2916). The sensitivity analysis also confirmed that horizontal pleiotropy was unlikely to bias the causality (e.g., UC and AS, MR-Egger: intercept p = 0.1326). The leave-one-out analysis also demonstrated that the observed links were not driven by SNP. No evidence of heterogeneity was found between the genetic variants (e.g., UC and AS, MR-Egger: Q statistic = 43.1297, I 2 <0.0001, p = 0.7434). Conclusion: Our results provide new evidence indicating there are positive causal effects of IBD on AS in the European population. We suggest that the features of inflammatory bowel disease in particular should be assessed in the diagnosis of ankylosing spondylitis. We also provide some advice for preventing and treating the two diseases.

BackgroundThis study aimed to explore the association between serum amino acids (AAs) levels and bone mineral density (BMD).MethodsWe performed a two-sample Mendelian randomization (MR) analysis to analyze the associations between the levels of eight AAs and BMD values by using summary-level genome-wide association study (GWAS) data. We applied the MR Steiger filtering method and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test to check for and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. The associations were estimated with the inverse variance weighted (IVW), MR-Egger, weighted median and MR Robust Adjusted Profile Score (MR.RAPS) methods.ResultsOur study found that genetically increased isoleucine (Ile) [IVW: effect = 0.1601, 95% confidence interval (CI) = 0.0604 ~ 0.2597, p = 0.0016] and valine (Val) levels (IVW: effect = 0.0953, 95% CI = 0.0251 ~ 0.1655, p = 0.0078) were positively associated with total body BMD (TB-BMD). The results also revealed that genetically increased tyrosine (Tyr) levels were negatively associated with TB-BMD (IVW: effect = -0.1091, 95% CI = -0.1863 ~ -0.0320, p = 0.0055).ConclusionsIn this study, associations between serum AA levels and BMD were established. These findings underscore the important role that serum AAs play in the development of osteoporosis and provide evidence that osteoporosis can be prevented and treated by the intake of certain AAs.

BackgroundIt remains unclear whether an increased risk of type 2 diabetes (T2D) affects the risk of osteoarthritis (OA).MethodsHere, we used two-sample Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on hip and knee OA. We identified single-nucleotide polymorphisms (SNPs) strongly associated with T2D, fasting glucose (FG), and 2-h postprandial glucose (2hGlu) from genome-wide association studies (GWAS). We used the MR inverse variance weighted (IVW), the MR–Egger method, the weighted median (WM), and the Robust Adjusted Profile Score (MR.RAPS) to reveal the associations of T2D, FG, and 2hGlu with hip and knee OA risks. Sensitivity analyses were also conducted to verify whether heterogeneity and pleiotropy can bias the MR results.ResultsWe did not find statistically significant causal effects of genetically increased T2D risk, FG, and 2hGlu on hip and knee OA (e.g., T2D and hip OA, MR–Egger OR = 1.1708, 95% CI 0.9469–1.4476, p = 0.1547). It was confirmed that horizontal pleiotropy was unlikely to bias the causality (e.g., T2D and hip OA, MR–Egger, intercept = −0.0105, p = 0.1367). No evidence of heterogeneity was found between the genetic variants (e.g., T2D and hip OA, MR–Egger Q = 30.1362, I2 &lt; 0.0001, p = 0.6104).ConclusionOur MR study did not support causal effects of a genetically increased T2D risk, FG, and 2hGlu on hip and knee OA risk.