Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis
BackgroundDiabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined...
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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.2024.1358144/full |
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| author | Zhangxin Ji Zhangxin Ji Chenxu Zhang Chenxu Zhang Jingjing Yuan Jingjing Yuan Qing He Qing He Xinyu Zhang Xinyu Zhang Dongmei Yang Dongmei Yang Na Xu Jun Chu Jun Chu Jun Chu |
| author_facet | Zhangxin Ji Zhangxin Ji Chenxu Zhang Chenxu Zhang Jingjing Yuan Jingjing Yuan Qing He Qing He Xinyu Zhang Xinyu Zhang Dongmei Yang Dongmei Yang Na Xu Jun Chu Jun Chu Jun Chu |
| author_sort | Zhangxin Ji |
| collection | DOAJ |
| description | BackgroundDiabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined.MethodsBased on the high-density genetic variation data at the genome-wide level, we evaluated the logical associations between 731 specific immune mediators and GDM using bidirectional Mendelian randomization (MR). The inverse variance weighted (IVW) was the main method employed for MR analysis. We performed multiple methods to verify the robustness and dependability of the MR results, and sensitivity measures were applied to rule out potential heterogeneity and horizontal pleiotropy.ResultsA substantial causal association between several immune mediators and GDM was detected. After FDR testing, HLA DR++ monocyte %leukocyte and HLA DR on plasmacytoid DC were shown to increase the risk of GDM; in contrast, CD127 on CD28+ CD45RA+ CD8br and CD19 on PB/PC were shown to attenuate the effect of GDM. Moreover, the progression of GDM has been shown to decrease the maternal levels of CD39+ activated Treg AC, CD39+ activated Treg %CD4 Treg, CD39+ resting Treg AC, CD39+ resting Treg %CD4 Treg, and CD39+ CD8BR %T cell.ConclusionsOur findings support a possible causal association between GDM and various immunophenotypes, thus facilitating the provision of multiple options for preventive recognition as well as for the diagnostic and therapeutic management of GDM in clinical practice. |
| first_indexed | 2024-04-24T07:44:25Z |
| format | Article |
| id | doaj.art-3f8ac13f407b45fca740464d31e77022 |
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| language | English |
| last_indexed | 2024-04-24T07:44:25Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-3f8ac13f407b45fca740464d31e770222024-04-19T04:41:35ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-04-011510.3389/fendo.2024.13581441358144Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysisZhangxin Ji0Zhangxin Ji1Chenxu Zhang2Chenxu Zhang3Jingjing Yuan4Jingjing Yuan5Qing He6Qing He7Xinyu Zhang8Xinyu Zhang9Dongmei Yang10Dongmei Yang11Na Xu12Jun Chu13Jun Chu14Jun Chu15Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaSchool of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaSchool of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaResearch and Technology Center, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaSchool of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaSchool of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaSchool of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaState Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Science and International Joint Laboratory on Tea Chemistry and Health Effects of Ministry of Education, Anhui Agricultural University, Hefei, Anhui, ChinaKey Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaResearch and Technology Center, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaInstitute of Surgery, Anhui Academy of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, ChinaBackgroundDiabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined.MethodsBased on the high-density genetic variation data at the genome-wide level, we evaluated the logical associations between 731 specific immune mediators and GDM using bidirectional Mendelian randomization (MR). The inverse variance weighted (IVW) was the main method employed for MR analysis. We performed multiple methods to verify the robustness and dependability of the MR results, and sensitivity measures were applied to rule out potential heterogeneity and horizontal pleiotropy.ResultsA substantial causal association between several immune mediators and GDM was detected. After FDR testing, HLA DR++ monocyte %leukocyte and HLA DR on plasmacytoid DC were shown to increase the risk of GDM; in contrast, CD127 on CD28+ CD45RA+ CD8br and CD19 on PB/PC were shown to attenuate the effect of GDM. Moreover, the progression of GDM has been shown to decrease the maternal levels of CD39+ activated Treg AC, CD39+ activated Treg %CD4 Treg, CD39+ resting Treg AC, CD39+ resting Treg %CD4 Treg, and CD39+ CD8BR %T cell.ConclusionsOur findings support a possible causal association between GDM and various immunophenotypes, thus facilitating the provision of multiple options for preventive recognition as well as for the diagnostic and therapeutic management of GDM in clinical practice.https://www.frontiersin.org/articles/10.3389/fendo.2024.1358144/fullgestational diabetes mellitusimmunitycausal inferencegenetic variationMendelian randomization |
| spellingShingle | Zhangxin Ji Zhangxin Ji Chenxu Zhang Chenxu Zhang Jingjing Yuan Jingjing Yuan Qing He Qing He Xinyu Zhang Xinyu Zhang Dongmei Yang Dongmei Yang Na Xu Jun Chu Jun Chu Jun Chu Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis Frontiers in Endocrinology gestational diabetes mellitus immunity causal inference genetic variation Mendelian randomization |
| title | Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis |
| title_full | Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis |
| title_fullStr | Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis |
| title_full_unstemmed | Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis |
| title_short | Is there a causal association between gestational diabetes mellitus and immune mediators? A bidirectional Mendelian randomization analysis |
| title_sort | is there a causal association between gestational diabetes mellitus and immune mediators a bidirectional mendelian randomization analysis |
| topic | gestational diabetes mellitus immunity causal inference genetic variation Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1358144/full |
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