{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:56:22Z","timestamp":1789656982973,"version":"4.0.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801631, 81871302"],"award-info":[{"award-number":["81801631, 81871302"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFE0207300"],"award-info":[{"award-number":["2018YFE0207300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z211100002521021"],"award-info":[{"award-number":["Z211100002521021"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Backgrounds<\/jats:title><jats:p>Observational studies have identified associations between smoking, alcohol use, body mass index (BMI), and the levels of vitamin D with primary biliary cholangitis (PBC). However, there was a lack of randomization control studies to estimate the causal relationship. This study was to investigate the causal estimates for the effects of those risk factors on PBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The genetic instrument variants were extracted from genome-wide association studies in European ancestry. Two-sample mendelian randomization (MR) and multivariable mendelian randomization were used to determine genetically causal estimates. Primary analyses consisted of random-effects and fix-mode inverse-variance-weighted methods, followed by secondary sensitivity analyses to verify the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study showed that BMI was a causal factor for PBC (OR 1.35; 95% CI=1.03-1.77; <jats:italic>p<\/jats:italic>=0.029). In addition, we found that serum vitamin D levels had a protective effect on PBC after adjusting for BMI (OR 0.51; 95% CI=0.32-0.84; <jats:italic>p<\/jats:italic>=0.007). However, we failed to identify evidence supporting that genetic causal effect of smoking and alcohol intake were associated with PBC in European countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results enriched findings from previous epidemiology studies and provided evidence from MR that serum vitamin D concentrations and BMI were independent causal factors for PBC, suggesting that ensuing vitamin D sufficiency and healthy lifestyles might be a cost-effective measure for early intervention for PBC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1055953","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T06:18:32Z","timestamp":1671517112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Low vitamin D concentrations and BMI are causal factors for primary biliary cholangitis: A mendelian randomization 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