Xu Senbao, Luo Qiuyan, He Jian, Chen Xiling, Li Simin, Bai Yang
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Cytobiology, Southern Medical University, Guangzhou, 510515, China.
Genes Nutr. 2023 Sep 11;18(1):14. doi: 10.1186/s12263-023-00734-1.
Previous observational studies have shown associations between vitamin Ds and FGIDS[Including irritable bowel syndrome(IBS) and functional dyspepsia(FD)]. However, the association is controversial and the causality remains unknown. In this study, two-sample MR was cited to explore the causal effect on FGIDS caused by vitamin D level and serum 25-hydroxyvitamin D.
The GWASs of vitaminD and 25-hydroxyvitamin D, with 57-99 strongly related SNPs were all obtained from UK biobank. The GWASs of IBS and FD were obtained from FinnGen biobank with respectively 187,028 and 194,071 participants involved. Fixed-effect inverse variance weighted regression was used to evaluate causal estimates. Other statistical methods such as MR Egger, weighted median estimation, maximum likelihood estimation and penalty-weighted median estimation are also used to verify the accuracy of the main results.
Measuring by the IVW method, our research indicated that no causal relationship was detected between vitamin D intake and Functional gastrointestinal disorders [IVW, OR(vitamin D-IBS) = 0.909, 95% CI 0.789-1.053, p = 0.2017); OR(vitamin D-FD) = 1.0662, 95% CI 0.9182-1.2380, p = 0.4000]. As for serum 25-hydroxyvitamin D, no causal relationship was detected on FD(IVW, OR(25-hydroxyvitamin D-FD) = 0.9635, 95% CI 0.8039-1.1546, p = 0.6869). Nevertheless, a negative causal relationship was revealed between 25-hydroxyvitamin D and IBS(IVW, OR(25-hydroxyvitamin D-IBS) = 0.832, 95% CI 0.696-0.995, p = 0.0436). Sensitive analysis supported the main findings but did not suggest bias due to pleiotropy.
Our Mendelian randomization analyses suggest a negative causal relationship between 25-hydroxyvitamin D and IBS. For each additional SD increase of genetically determined 25-hydroxyvitamin D levels, the risk of IBS decreased by 16.8%.
既往观察性研究表明维生素D与功能性胃肠疾病[包括肠易激综合征（IBS）和功能性消化不良（FD）]之间存在关联。然而，这种关联存在争议，因果关系尚不清楚。在本研究中，采用两样本孟德尔随机化方法探讨维生素D水平和血清25-羟维生素D对功能性胃肠疾病的因果效应。
维生素D和25-羟维生素D的全基因组关联研究（GWAS），包含57-99个强相关单核苷酸多态性（SNP），均来自英国生物银行。IBS和FD的GWAS来自芬兰生物银行，分别涉及187,028名和194,071名参与者。采用固定效应逆方差加权回归评估因果估计值。还使用了其他统计方法，如孟德尔随机化Egger回归、加权中位数估计、最大似然估计和惩罚加权中位数估计来验证主要结果的准确性。
采用逆方差加权（IVW）方法测量，我们的研究表明维生素D摄入量与功能性胃肠疾病之间未检测到因果关系[IVW，比值比（维生素D-IBS）=0.909，95%可信区间0.789-1.053，p=0.2017）；比值比（维生素D-FD）=1.0662，95%可信区间0.9182-1.2380，p=0.4000]。至于血清25-羟维生素D，未检测到与FD的因果关系（IVW，比值比（25-羟维生素D-FD）=0.9635，95%可信区间0.8039-1.1546，p=0.6869）。然而，25-羟维生素D与IBS之间显示出负向因果关系（IVW，比值比（25-羟维生素D-IBS）=0.832，95%可信区间0.696-0.995，p=0.0436）。敏感性分析支持主要发现，但未提示因多效性导致的偏倚。
我们的孟德尔随机化分析表明25-羟维生素D与IBS之间存在负向因果关系。基因决定的25-羟维生素D水平每增加一个标准差，IBS风险降低16.8%。
