This study provides genetic evidence for unidirectional causal effects of thyroid function on specific endometriosis phenotypes in Europeans, with no reverse causality.
Abstract
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.
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.
Jiawei Shi, Weijie Jiang, Hui Chen et al.· Frontiers in Endocrinology· 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
An independent observational association between hyperthyroidism and an increased risk of HDP is demonstrated, and supportive genetic evidence for a possible bidirectional association between genetically predicted TSH and HDP is provided.
Yu He, Ye-shen Zhang, Yanxin Sun et al.· International journal of gyn...· 0 citations
Objectives This study is aimed at comprehensively understanding genetically causal associations between some platelet indices (PIs) and rheumatoid arthritis (RA). Methods Genetic summary statistics for the 4 types of PIs and RA were derived from Neale Lab, FinnGen, and MRC‐IEU consortium. Two‐sample Mendelian randomization (TSMR) analysis was utilized to infer the bidirectional causality with the implementation of the inverse‐variance weighted (IVW), weighted median (WM), weighted mode, and MR‐Egger methods. Sensitivity analysis with leave‐one‐out method was conducted to assess the robustness of the observed causal estimates. Results TSMR results indicated that the genetically‐determined plateletcrit (PCT) had a causal association with the higher risk of RA (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.01, 1.29, p = 0.012) and seropositive RA (OR = 1.03, 95% CI: 1.01, 1.21, p = 0.003). Both WM method and sensitivity analysis supported that the observed causal estimates were reliable. In the reverse MR analysis, genetic susceptibility leading to RA (Beta [se] = −0.012 [0.006], p = 0.037) was causally related to the decrease in mean platelet volume (MPV). Conclusions Our study reveals a positive causal association between PCT and the risk of RA, and that genetic susceptibility to RA is causally associated with a reduced MPV. This provides a reference for further studies on the exploration of mechanisms of platelets in the pathogenesis of RA.
Xu-Yan Shen, Jiaying Sun, Xin Wang et al.· International Journal of Gen...· 0 citations
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
The association between immunocyte phenotypes and dilated cardiomyopathy (DCM) has been explored, however the exact pathogenesis of the relationship between immune cells and DCM is unclear. This bidirectional two-sample Mendelian randomization (MR) research aims to further validate the causal link between 731 immunocyte phenotypes and DCM. Summary statistics from a genome-wide association study data of individuals with European ancestry were utilized, including 1444 DCM cases and 353,937 controls, as well as 3757 European adults for the 731 immunocyte phenotypes. Causal effects were estimated using inverse variance weighted, MR-Egger regression, weight median estimator, weighted mode, and simple mode. Sensitivity analysis was conducted to confirm data robustness and feasibility. Based on the inverse variance weighted findings, 14 immunocyte phenotypes were risk factors for DCM (P < .05, odds ratio [OR] > 1), while 15 immunocyte phenotypes exhibited a protective effect on DCM (P < .05, OR < 1). The results of reverse MR analysis suggested evidence that DCM occurrence might elevate the levels of 17 immunocyte phenotypes (P < .05, OR > 1) and decrease the levels of 9 immunocyte phenotypes (P < .05, OR < 1). Our research indicated that CD28 on secreting regulatory T cell could mitigate the occurrence of DCM, and reciprocally, the progression of DCM could reduce the level of CD28 on secreting regulatory T cell. This study confirmed the bidirectional genetic predictive relationship between immunocyte phenotypes and DCM, underscoring the complex interplay between DCM and the immune system.
Wenshuai Feng, Xindi Chang, Qiaozhi Li et al.· Medicine· 0 citations
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