Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study
BackgroundGender differences existed in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex ho...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1272746/full |
| _version_ | 1797215804093104128 |
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| author | Fei Zou Fei Zou Yaxian Hu Mengmeng Xu Mengmeng Xu Su Wang Su Wang Zengrong Wu Zengrong Wu Feihong Deng Feihong Deng |
| author_facet | Fei Zou Fei Zou Yaxian Hu Mengmeng Xu Mengmeng Xu Su Wang Su Wang Zengrong Wu Zengrong Wu Feihong Deng Feihong Deng |
| author_sort | Fei Zou |
| collection | DOAJ |
| description | BackgroundGender differences existed in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear.MethodBased on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation.ResultsE2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046).ConclusionFindings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD. |
| first_indexed | 2024-04-24T11:35:53Z |
| format | Article |
| id | doaj.art-0e049c7303b84b07a36639c4109fb70f |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-24T11:35:53Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-0e049c7303b84b07a36639c4109fb70f2024-04-10T05:13:13ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-04-011510.3389/fendo.2024.12727461272746Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization studyFei Zou0Fei Zou1Yaxian Hu2Mengmeng Xu3Mengmeng Xu4Su Wang5Su Wang6Zengrong Wu7Zengrong Wu8Feihong Deng9Feihong Deng10Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaResearch Center of Digestive Disease, Central South University, Changsha, Hunan, ChinaDepartment of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaResearch Center of Digestive Disease, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaResearch Center of Digestive Disease, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaResearch Center of Digestive Disease, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaResearch Center of Digestive Disease, Central South University, Changsha, Hunan, ChinaBackgroundGender differences existed in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear.MethodBased on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation.ResultsE2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046).ConclusionFindings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.https://www.frontiersin.org/articles/10.3389/fendo.2024.1272746/fullinflammatory bowel diseasesex hormoneestradiolprogesteronetestosteroneMendelian randomization |
| spellingShingle | Fei Zou Fei Zou Yaxian Hu Mengmeng Xu Mengmeng Xu Su Wang Su Wang Zengrong Wu Zengrong Wu Feihong Deng Feihong Deng Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study Frontiers in Endocrinology inflammatory bowel disease sex hormone estradiol progesterone testosterone Mendelian randomization |
| title | Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study |
| title_full | Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study |
| title_fullStr | Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study |
| title_full_unstemmed | Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study |
| title_short | Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study |
| title_sort | associations between sex hormones receptors binding proteins and inflammatory bowel disease a mendelian randomization study |
| topic | inflammatory bowel disease sex hormone estradiol progesterone testosterone Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1272746/full |
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