Causal associations of 25-hydroxyvitamin D with functional gastrointestinal disorders: a two-sample Mendelian randomization study

Senbao Xu; Qiuyan Luo; Jian He; Xiling Chen; Simin Li; Yang Bai

doi:10.1186/s12263-023-00734-1

Causal associations of 25-hydroxyvitamin D with functional gastrointestinal disorders: a two-sample Mendelian randomization study

Genes Nutr. 2023 Sep 11;18(1):14. doi: 10.1186/s12263-023-00734-1.

Authors

Senbao Xu¹, Qiuyan Luo¹, Jian He¹, Xiling Chen¹, Simin Li², Yang Bai³

Affiliations

¹ Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
² Department of Cytobiology, Southern Medical University, Guangzhou, 510515, China.
³ Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 13925001665@163.com.

Abstract

Background: 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.

Method: 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.

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.

Conclusions: 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%.

Keywords: 25-hydroxyvitamin D; Functional dyspepsia; Genetic variants; Irritable bowel syndrome; Mendelian randomization; Vitamin D.

Abstract

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