Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines
BackgroundPrevious observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to invest...
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Frontiers Media S.A.
2024-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1376139/full |
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| author | Shuyun Wu Jiazhi Yi Bin Wu |
| author_facet | Shuyun Wu Jiazhi Yi Bin Wu |
| author_sort | Shuyun Wu |
| collection | DOAJ |
| description | BackgroundPrevious observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD.MethodsGenome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations.ResultsGenetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655–0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888–0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857–0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830–0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094–1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD.ConclusionOur results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD. |
| format | Article |
| id | doaj-art-83eeacaebab04302bc563ae17c71ff98 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-83eeacaebab04302bc563ae17c71ff982025-08-20T03:31:19ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-05-011510.3389/fendo.2024.13761391376139Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokinesShuyun WuJiazhi YiBin WuBackgroundPrevious observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD.MethodsGenome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations.ResultsGenetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655–0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888–0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857–0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830–0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094–1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD.ConclusionOur results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD.https://www.frontiersin.org/articles/10.3389/fendo.2024.1376139/fullthyroid functionhypothyroidisminflammatory bowel diseaseIP-10Mendelian randomization |
| spellingShingle | Shuyun Wu Jiazhi Yi Bin Wu Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines Frontiers in Endocrinology thyroid function hypothyroidism inflammatory bowel disease IP-10 Mendelian randomization |
| title | Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines |
| title_full | Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines |
| title_fullStr | Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines |
| title_full_unstemmed | Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines |
| title_short | Causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines |
| title_sort | causal associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines |
| topic | thyroid function hypothyroidism inflammatory bowel disease IP-10 Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1376139/full |
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