Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study
Although inflammation may disrupt immunoendocrine crosstalk essential for female reproductive function, causal links to disorders like polycystic ovary syndrome (PCOS) and endometriosis remain unestablished. This study aimed to utilise Mendelian randomisation (MR) methods to explore causal associati...
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2024-12-01
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| author | Simon Alesi Helena Teede Lisa Moran Joanne Enticott Kushan De Silva Aya Mousa |
| author_facet | Simon Alesi Helena Teede Lisa Moran Joanne Enticott Kushan De Silva Aya Mousa |
| author_sort | Simon Alesi |
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| description | Although inflammation may disrupt immunoendocrine crosstalk essential for female reproductive function, causal links to disorders like polycystic ovary syndrome (PCOS) and endometriosis remain unestablished. This study aimed to utilise Mendelian randomisation (MR) methods to explore causal associations between serum inflammatory markers and common reproductive disorders, aiming to identify novel mechanisms and potential avenues for treatment. Total causal effects of serum inflammatory markers (interleukins, monocyte chemoattractant protein-1, etc.) on female reproductive disorders in large sample cohorts of Finnish ancestry were assessed using univariable two-sample MR methods, including the inverse variance weighted (IVW) method as the primary analysis, with relevant quality assessments (e.g., leave-one out, heterogeneity, and horizontal pleiotropy testing). The main outcome measures were PCOS (642 cases and 118,228 controls) and endometriosis (8288 cases and 68,969 controls) from the FINNGEN cohort. Monocyte chemoattractant protein-1/C-C motif chemokine ligand demonstrated a positive causal association with polycystic ovary syndrome (odds ratio [95% CI]: 1.48 [1.10, 2.00], <i>p</i> = 0.0097), while higher interleukin-9 levels were positively associated with endometriosis (1.15 [1.02, 1.30], <i>p</i> = 0.0277), both via the IVW method. These markers should be investigated as key candidates for future research into the mechanistic pathways underpinning these conditions. |
| format | Article |
| id | doaj-art-219d9d2aa013442bb53e2b0b302d43f2 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-219d9d2aa013442bb53e2b0b302d43f22024-12-27T14:13:45ZengMDPI AGBiomolecules2218-273X2024-12-011412154410.3390/biom14121544Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation StudySimon Alesi0Helena Teede1Lisa Moran2Joanne Enticott3Kushan De Silva4Aya Mousa5Monash Centre for Health Research and Implementation (MCHRI), Monash University, Clayton, VIC 3800, AustraliaMonash Centre for Health Research and Implementation (MCHRI), Monash University, Clayton, VIC 3800, AustraliaMonash Centre for Health Research and Implementation (MCHRI), Monash University, Clayton, VIC 3800, AustraliaMonash Centre for Health Research and Implementation (MCHRI), Monash University, Clayton, VIC 3800, AustraliaDepartment of Radiation Sciences, Faculty of Medicine, Umeå University, SE-901 87 Umeå, SwedenMonash Centre for Health Research and Implementation (MCHRI), Monash University, Clayton, VIC 3800, AustraliaAlthough inflammation may disrupt immunoendocrine crosstalk essential for female reproductive function, causal links to disorders like polycystic ovary syndrome (PCOS) and endometriosis remain unestablished. This study aimed to utilise Mendelian randomisation (MR) methods to explore causal associations between serum inflammatory markers and common reproductive disorders, aiming to identify novel mechanisms and potential avenues for treatment. Total causal effects of serum inflammatory markers (interleukins, monocyte chemoattractant protein-1, etc.) on female reproductive disorders in large sample cohorts of Finnish ancestry were assessed using univariable two-sample MR methods, including the inverse variance weighted (IVW) method as the primary analysis, with relevant quality assessments (e.g., leave-one out, heterogeneity, and horizontal pleiotropy testing). The main outcome measures were PCOS (642 cases and 118,228 controls) and endometriosis (8288 cases and 68,969 controls) from the FINNGEN cohort. Monocyte chemoattractant protein-1/C-C motif chemokine ligand demonstrated a positive causal association with polycystic ovary syndrome (odds ratio [95% CI]: 1.48 [1.10, 2.00], <i>p</i> = 0.0097), while higher interleukin-9 levels were positively associated with endometriosis (1.15 [1.02, 1.30], <i>p</i> = 0.0277), both via the IVW method. These markers should be investigated as key candidates for future research into the mechanistic pathways underpinning these conditions.https://www.mdpi.com/2218-273X/14/12/1544mendelian randomisationinflammationendometriosispolycystic ovary syndrome (PCOS)interleukinsmonocyte chemoattractant protein-1/C-C motif ligand-2 (MCP-1/CCL2) |
| spellingShingle | Simon Alesi Helena Teede Lisa Moran Joanne Enticott Kushan De Silva Aya Mousa Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study Biomolecules mendelian randomisation inflammation endometriosis polycystic ovary syndrome (PCOS) interleukins monocyte chemoattractant protein-1/C-C motif ligand-2 (MCP-1/CCL2) |
| title | Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study |
| title_full | Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study |
| title_fullStr | Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study |
| title_full_unstemmed | Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study |
| title_short | Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study |
| title_sort | exploring causal associations between serum inflammatory markers and female reproductive disorders a mendelian randomisation study |
| topic | mendelian randomisation inflammation endometriosis polycystic ovary syndrome (PCOS) interleukins monocyte chemoattractant protein-1/C-C motif ligand-2 (MCP-1/CCL2) |
| url | https://www.mdpi.com/2218-273X/14/12/1544 |
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