Aug 2026· Actas espanolas de psiquiatria· Vol 54 4, pp.
1257-1268
· 0 citations
Medicine
TL;DR
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.
Abstract
Background
Observational studies have reported associations between antidepressant use and thyroid dysfunction; however, confounding precludes firm causal inference. This study aimed to evaluate the potential causal association between genetically predicted antidepressant use and the risks of Hashimoto's thyroiditis, hypothyroidism and thyroid cancer using Mendelian randomisation (MR).
Methods
Publicly available genome-wide association study (GWAS) summary statistics were used, with genetically predicted antidepressant use as the exposure and Hashimoto's thyroiditis, hypothyroidism and thyroid cancer as the outcomes. Following data harmonisation, 13 single nucleotide polymorphisms (SNPs) meeting the prespecified significance threshold were selected as instrumental variables. The mean F statistic was 24.12 (range, 20.96-29.98), indicating that weak-instrument bias was unlikely. Inverse variance weighted (IVW) was used for the primary analysis, with MR-Egger regression, weighted-median and mode-based methods used in sensitivity analyses. Cochran's Q test was used to assess heterogeneity, and the MREgger intercept was used to assess directional horizontal pleiotropy.
Results
Genetically predicted antidepressant use was positively associated with the risk of Hashimoto's thyroiditis (IVW: odds ratio [OR] = 1.483, 95% confidence interval [CI]: 1.176-1.871; p = 0.001). A weak but statistically significant positive association was also observed for hypothyroidism (IVW: OR = 1.012, 95% CI: 1.002-1.023; p = 0.025). The directions of effect were generally consistent across sensitivity analyses. No evidence of an association with thyroid cancer was identified (IVW: p = 0.407). No evidence of bias was found in the heterogeneity test and the horizontal pleiotropy (p > 0.05), and the leave-one-out analysis confirmed the robustness of the results.
Conclusions
This study provides genetic evidence of potential associations between antidepressant use and increased risks of Hashimoto's thyroiditis and hypothyroidism. These findings support consideration of thyroidfunction monitoring in patients receiving antidepressant treatment, particularly those with pre-existing thyroid risk factors.
Accumulating observational evidence suggests an association between thyroid function and endometriosis, though the causal relationship remains unclear. To investigate potential bidirectional causal relationships, including for endometriosis subtypes, we conducted a bidirectional 2-sample Mendelian randomization (MR) analysis utilizing summary genetic data. Data sources included the ThyroidOmics Consortium (free thyroxine [FT4], thyroid-stimulating hormone [TSH], subclinical hypothyroidism, subclinical hyperthyroidism: N = 72,167, thyroid peroxidase antibody [TPOAb]: N = 18,297), IEU database (N = 3,37,159), and FinnGen Consortium R9 (8288 cases and 68,969 controls). The inverse variance weighted method served as the primary analysis, supplemented by sensitivity analyses to evaluate pleiotropy and heterogeneity, alongside subgroup analyses. Forward MR analysis revealed that genetically predicted FT4 was negatively associated with total endometriosis (odds ratio [OR] = 0.886, 95% confidence interval [CI]: 0.794–0.989, P = .031). Furthermore, overt hypothyroidism (OR = 0.227, 95% CI: 0.056–0.916, P = .037) and subclinical hypothyroidism (OR = 0.859, 95% CI: 0.762–0.969, P = .013) were negatively associated with endometriosis with occurring infertility, whereas subclinical hyperthyroidism was negatively associated with the uterine subtype (OR = 0.919, 95% CI: 0.863–0.979, P = .008). Conversely, TSH levels within the normal range were positively associated with the uterine subtype (OR = 1.195, 95% CI: 1.031–1.386, P = .018). Reverse MR analysis did not reveal any causality between endometriosis and thyroid function. This study provides genetic evidence for unidirectional causal effects of thyroid function on specific endometriosis phenotypes in Europeans, with no reverse causality. These findings warrant replication in independent cohorts and well-designed prospective studies.
Jiahuan Luo, Ruopeng Zhang, Mengjie Song et al.· Medicine· 1 citation
Genetic evidence supporting a causal role for depression in the etiology of late-onset AD is provided, a link not observed for other major psychiatric disorders tested and highlighted the specific importance of managing depression as a potential strategy for mitigating AD risk.
Background
Dupuytren's disease (DD) is associated with metabolic and lifestyle traits. However, these associations remain uncertain because exposures frequently cluster, and conventional studies are vulnerable to residual confounding and reverse causation.
Methods
A two-sample Mendelian randomization (MR) analysis using genetic instruments for diabetes, obesity-related, smoking, and alcohol-related traits from genome-wide association studies of large European ancestry was conducted. Summary statistics of DD were obtained from UK Biobank and FinnGen and combined using meta-analysis. Multiplicative random-effects inverse variance weighted MR was used as the primary method, with complementary sensitivity analyses to test robustness.
Results
Genetic liability for diabetes was associated with a higher risk of DD (meta-analyzed odds ratio [OR], 1.0157; 95% confidence interval [CI], 1.0070-1.0245; P<0.001). Genetically predicted alcohol intake was also positively associated with DD (alcohol intake OR, 1.0150; 95% CI, 1.0087-1.0212; P<0.001; drinks per week OR, 1.0062; 95% CI, 1.0015-1.0110; P=0.0103). However, we found no convincing evidence that obesity traits or smoking intensity had causal effects on DD. Sensitivity analyses were directionally consistent, the instruments were adequately strong, and there was no substantial evidence of horizontal pleiotropy for the main associations. Although the observed effect sizes were modest, consistent with the multifactorial nature of DD, supporting directional risk associations rather than large individual-level effects.
Conclusion
This MR study supported diabetes liability and higher alcohol intake as causal risk factors for DD, whereas genetically proxied obesity and smoking traits showed no clear causal effects. These findings suggest that better glycemic management and lower alcohol exposure may help reduce the risk of DD.
Heng Tian, Ling Hong, Wenlai Guo et al.· Korean Journal of Family Med...· 0 citations
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.
Jiawei Shi, Weijie Jiang, Hui Chen et al.· Frontiers in Endocrinology· 0 citations
INTRODUCTION
To perform a two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between polymyalgia rheumatica (PMR) and hypothyroidism.
METHODS
Genome-wide association study (GWAS) data for PMR and hypothyroidism were obtained from publicly available databases. The inverse variance weighted (IVW) method was primarily used to evaluate the potential causal effect of PMR-related traits on the risk of hypothyroidism. To assess the robustness of the findings, additional methods, including the weighted median (WME), MR-Egger (ME), simple mode (SM), and weighted mode (WM), were employed. Sensitivity analyses were performed using the MR-PRESSO method and Cochran's Q test to detect potential heterogeneity and horizontal pleiotropy. Furthermore, a reverse MR analysis was performed to investigate the possibility of reverse causality.
RESULTS
IVW analysis demonstrated a significant causal relationship between PMR and hypothyroidism (OR=1.373, 95%CI:1.287-1.465, P=5.84×10⁻²²). In contrast, ME produced a non-significant result (OR=0.880, 95%CI:0.602-1.286, P=0.577). WME supported IVW findings (OR=1.373, 95%CI:1.280-1.480, P=8.97×10⁻¹⁸), as did WM (OR=1.410, 95%CI:1.243-1.599, P=0.013) and the SM (OR=1.398, 95%CI:1.240-1.575, P=0.012). Collectively, these findings provide evidence supporting a causal effect of PMR on the risk of hypothyroidism. Reverse MR analysis using the IVW method also indicated a significant causal association (OR=1.195, 95%CI:1.135-1.258, P=9.35×10-12). However, both ME regression and IVW heterogeneity tests showed evidence of heterogeneity (P=3.16×10⁻³⁸; P=4.11×10⁻³⁸). The ME analysis revealed no evidence of horizontal pleiotropy (P=0.615).
DISCUSSION
A study suggested that hypothyroidism-induced myopathic changes may mimic or exacerbate PMR symptoms, potentially leading to misdiagnosis or overtreatment with corticosteroids. Importantly, recurrence of PMR symptoms has been observed after thyroid hormone replacement, even in the presence of normalized thyroid function. These findings underscore a potential bidirectional relationship between PMR and hypothyroidism. In addition, some researchers held that HLA-B8 and DR3 may be a significant indicator to assess the association between these diseases; however, some observations suggest that it may not serve as a specific risk marker for PMR or its complications.
CONCLUSION
PMR is closely associated with the development of hypothyroidism; the risk of hypothyroidism increases as PMR progresses; on the other hand, advancing hypothyroidism may also raise the likelihood of developing PMR.
Kaige Gao, Xin Yang, Zhenyu Wang et al.· Current Rheumatology Reviews· 0 citations