Aug 2026· Frontiers in Endocrinology· Vol 17· 0 citations· 26 references
Medicine
TL;DR
This integrated genetic and clinical analysis found no robust evidence that genetic liability to AIHT materially affects overall endometriosis risk or vice versa in the datasets analyzed, and no clear clinical association between confirmed endometriosis and AIHT or thyroid autoimmunity.
Abstract
Background Observational studies have reported comorbidity between autoimmune thyroid disease and endometriosis, but whether this reflects a direct causal relationship or shared susceptibility remains unclear. We evaluated the bidirectional relationship between autoimmune hypothyroidism (AIHT) and endometriosis using Mendelian randomization (MR) and an independent clinical cohort. Methods Genome-wide association study (GWAS) summary statistics were obtained for AIHT from a FinnGen R12–UK Biobank meta-analysis and for endometriosis from GWAS Catalog study GCST90205183. Genome-wide significant instruments underwent linkage disequilibrium clumping, genome-build liftover, and harmonization. Inverse-variance weighted (IVW) analysis was primary, with weighted median and MR-Egger analyses as complements. Sensitivity analyses included heterogeneity and MR-Egger intercept tests, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, phenome-wide association study-informed filtering, and exclusion of the human leukocyte antigen region. Clinical associations were assessed using multivariable logistic regression. Results After harmonization, 248 single-nucleotide polymorphisms (SNPs) were included for AIHT-to-endometriosis analysis and 26 for endometriosis-to-AIHT analysis. IVW showed no association of genetic liability to AIHT with endometriosis (odds ratio [OR] = 0.985, 95% confidence interval [CI]: 0.957–1.014, P = 0.315) or of genetic liability to endometriosis with AIHT (OR = 0.999, 95% CI: 0.951–1.049, P = 0.968). MR-PRESSO global tests were significant in both directions, indicating pleiotropic heterogeneity. No forward outlier was identified; removal of the reverse-direction outlier rs2433340 did not materially alter the estimate (corrected OR = 1.007, 95% CI: 0.960–1.056, P = 0.769). The cohort included 7,825 women: 853 with confirmed endometriosis and 6,972 diagnosis-negative controls. Endometriosis was not associated with AIHT after adjustment (OR = 0.753, 95% CI: 0.440–1.287, P = 0.299); findings were also non-significant for thyroid autoimmunity, thyroid peroxidase antibody positivity, thyroglobulin antibody positivity, and hypothyroidism. Conclusion This integrated genetic and clinical analysis found no robust evidence that genetic liability to AIHT materially affects overall endometriosis risk or vice versa in the datasets analyzed, and no clear clinical association between confirmed endometriosis and AIHT or thyroid autoimmunity. Small effects and sex- or subtype-specific associations cannot be excluded.
This study provides genetic evidence for unidirectional causal effects of thyroid function on specific endometriosis phenotypes in Europeans, with no reverse causality.
Jiahuan Luo, Ruopeng Zhang, Mengjie Song et al.· Medicine· 1 citation
Evidence is provided supporting a causal effect of PMR on the risk of hypothyroidism and suggesting that hypothyroidism-induced myopathic changes may mimic or exacerbate PMR symptoms, potentially leading to misdiagnosis or overtreatment with corticosteroids.
Kaige Gao, Xin Yang, Zhenyu Wang et al.· Current Rheumatology Reviews· 0 citations
Background/Objectives: Epidemiological studies link autoimmune diseases (AIDs) to follicular lymphoma (FL) risk, but their shared genetic architecture and causal mechanisms remain unclear. Methods: A two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships between 15 AIDs and FL. Pleiotropic loci were identified through the Pleiotropy Analysis under Composite Null (PLACO). Bayesian colocalization analysis, functional mapping, and Multi-marker Analysis of GenoMic Annotation were applied to fine-map shared genetic variants and identify their target genes. Summary data-based MR was used with multitissue expression quantitative trait locus data to infer causal effects of gene expression. HyPrColoc analysis was applied to decipher shared genetic regulation of immune cell phenotypes. Results: MR revealed that rheumatoid arthritis increased FL risk (ORIVW = 1.55, nominal p = 7.16 × 10−5, FDR-corrected p = 1.07 × 10−3), whereas composite autoimmune disease reduced FL risk (ORIVW = 0.70, nominal p = 4.61 × 10−5, FDR-corrected p = 6.92 × 10−4). Hypothyroidism showed only a nominally suggestive protective trend (ORIVW = 0.88, nominal p = 0.015), which did not survive Benjamini–Hochberg multiple-testing correction (FDR-corrected p = 0.075). Fifty-five pleiotropic loci shared between FL and AIDs were identified, among which key loci such as 1p36.32, 6p21.32, 17p13.1, and 11q23.3 exhibited strong colocalization evidence. Core pleiotropic genes (e.g., TNFRSF14, MMEL1, CXCR5, and RNASET2) were prioritized, which implicated pathways related to MHC class II antigen presentation, interferon signaling, and T cell activation. HyPrColoc analysis demonstrated that these loci colocalized with the expression of immune receptors, including BAFF-R on B cells and HVEM (TNFRSF14) on naïve CD8+ T cells. Conclusions: Our study identifies divergent causal effects of selected AIDs on FL risk and demonstrates localized pleiotropy at key loci, providing novel insights into shared immunogenetic mechanisms.
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) poses a major global health burden, but its relationship with serum uric acid (SUA) remains controversial. This study combined meta-analysis and Mendelian randomization (MR) to evaluate the observational association and potential causal relationship between SUA and COPD.
METHODS
We systematically searched PubMed, Embase, Web of Science, CNKI, and Wanfang Data for observational studies comparing SUA levels between COPD patients and healthy controls published up to December 2025. Meta-analysis was performed using a random-effects model to calculate mean differences (MD) and 95% confidence intervals (CI), followed by subgroup analyses. This meta-analysis has been registered with PROSPERO under the registration number CRD420251234511. Two-sample bidirectional MR analysis was conducted using publicly available GWAS summary data, with inverse variance weighting (IVW) as the primary method, supplemented by weighted median, MR-Egger regression, and sensitivity analyses.
RESULTS
The meta-analysis included 22 studies, comprising a total of 3739 COPD patients and 2778 healthy controls. Results showed that SUA levels were significantly higher in stable COPD patients compared to healthy controls (MD: 1.19 mg/dL, 95% CI: 0.83-1.55, P < 0.00001). Patients with acute exacerbation of COPD (AECOPD) exhibited even higher uric acid levels (MD: 1.30 mg/dL, 95% CI: 0.36-2.24, P < 0.00001), and SUA levels were significantly higher in severe COPD patients compared to those with mild-to-moderate COPD (MD: 1.18 mg/dL, 95% CI: 0.76-1.60, P = 0.02). Bidirectional MR analysis revealed that genetically predicted higher SUA levels were causally associated with reduced COPD risk (IVW: OR: 0.883, 95% CI: 0.811-0.961, P = 0.004). Reverse MR analysis found no significant causal effect of COPD on uric acid levels (P > 0.05). Sensitivity analyses supported the robustness of the MR findings.
CONCLUSION
Observational evidence indicated elevated SUA in COPD, especially during exacerbations, while genetically predicted higher SUA showed a modest protective effect. These findings suggest a complex, dual role of uric acid. However, observational associations may be confounded by reverse causality, and the MR estimates-derived from East Asian populations-are method-sensitive. Current evidence does not yet support altering uric acid management in COPD, and further prospective and interventional studies across diverse populations are warranted.
Aiju Su, Yunpeng Xu, Xue Han et al.· BMC Pulmonary Medicine· 0 citations
Numerous observational studies have suggested a potential shared genetic background between inflammatory bowel disease (IBD) and IgA vasculitis (IgAV). However, the causal relationship between these 2 conditions remains poorly understood. We performed large-scale two-sample and multivariable Mendelian randomization (MR) analyses (MVMR) to examine whether there is a causal relationship between IBD and IgAV. We employed 4 distinct approaches, including MR-Egger, weighted median, random-effects inverse-variance weighted (IVW), and weighted mode, to conduct the MR analysis. The univariable MR analysis demonstrated that IBD and Crohn disease (CD) were associated with an increased risk of IgAV in the International Inflammatory Bowel Disease Genetics Consortium, with an odds ratio (OR) of 1.17 (95% confidence interval [CI]: 1.06–1.28, PIVW = .001) for IBD and an OR of 1.12 (95% CI: 1.01–1.24, PIVW = .016) for CD. Ulcerative colitis was associated with an increased risk of IgAV, which was considered suggestive after Bonferroni correction, with an OR of 1.12 (95% CI: 1.01–1.24, PIVW = .028). Consistent results were observed after adjusting for potential confounders (drug allergy and upper respiratory tract infection) in MVMR. IBD, ulcerative colitis, and CD were associated with an increased risk of IgAV, with an OR of 1.20 (95% CI: 1.08–1.34, PIVW = .001), 1.20 (95% CI: 1.07–1.35, PIVW = .002), and 1.13 (95% CI: 1.03–1.25, PIVW = .0012). Our study identifies a causal relationship between IBD and IgAV, particularly between CD and IgAV, suggesting that IBD is a potential precursor to IgAV rather than the converse. Further studies on the common mechanisms of these 2 diseases are needed.
Bingqing Yi, Yaoyue Luo, Hong Li et al.· Medicine· 0 citations
Genetic evidence of potential associations between antidepressant use and increased risks of Hashimoto's thyroiditis and hypothyroidism is provided, and support consideration of thyroidfunction monitoring in patients receiving antidepressant treatment, particularly those with pre-existing thyroid risk factors.
Yingxian Ling, Qisong Chen· Actas espanolas de psiquiatr...· 0 citations
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