Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Clinical Innovation and Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Front Endocrinol (Lausanne). 2024 Oct 2;15:1364027. doi: 10.3389/fendo.2024.1364027. eCollection 2024.
Thyroid hormones have actions on cartilage, whereas the association between thyroid hormone related diseases and osteoarthritis (OA) are unclear. This study aims to investigate the association between thyrotoxicosis and OA.
Summary-level genetic data of thyrotoxicosis were obtained from FinnGen cohorts (nCase = 10,569, nControl = 762,037). Summary-level data of OA were obtained from a large-scale genome-wide association study of UK Biobank (nCase = 40,659, nControl = 756,338). Single nucleotide polymorphisms (SNPs) robustly associated with thyrotoxicosis or OA were used as genetic instruments. A two-sample bidirectional Mendelian randomization (MR) analysis was designed to assess the effect of genetic predisposition of thyrotoxicosis on OA risk, as well as the reverse their relationship. The causal effect was estimated by Inverse-variance weighted method, with weighted median and MR-Egger as supplementary methods.
Genetic predisposition of thyrotoxicosis was associated with the onset of knee OA (autoimmune hyperthyroidism: odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.03-1.07, FDR < 0.001; thyrotoxicosis: OR: 1.05, 95% CI: 1.02-1.08, FDR = 0.016; thyrotoxicosis with diffuse goitre: OR: 1.04, 95% CI: 1.02-1.07, FDR = 0.003; other and/or unspecified thyrotoxicosis: OR: 1.05, 95% CI: 1.02-1.09, FDR = 0.003), whereas thyrotoxicosis was not associated with hip OA. In reverse MR analysis, genetic predisposition to OA was not associated with thyrotoxicosis. No pleiotropy was identified in the MR analyses. Sensitivity analyses indicated the robustness of the MR estimates.
This study provides MR evidence supporting causal association of thyrotoxicosis with knee OA in European population, whereas OA may have no causal effects on thyrotoxicosis.
甲状腺激素对软骨有作用，而甲状腺激素相关疾病与骨关节炎（OA）之间的关系尚不清楚。本研究旨在探讨甲状腺毒症与 OA 之间的关系。
从芬兰人群 FinnGen 队列中获得甲状腺毒症的汇总水平遗传数据（nCase=10569，nControl=762037）。从英国生物银行的一项大规模全基因组关联研究中获得 OA 的汇总水平数据（nCase=40659，nControl=756338）。将与甲状腺毒症或 OA 稳健相关的单核苷酸多态性（SNP）用作遗传工具。设计了两样本双向 Mendelian 随机化（MR）分析，以评估甲状腺毒症遗传易感性对 OA 风险的影响，以及它们之间的反向关系。采用逆方差加权法估计因果效应，加权中位数和 MR-Egger 作为补充方法。
甲状腺毒症的遗传易感性与膝关节 OA 的发病有关（自身免疫性甲状腺功能亢进症：比值比[OR]：1.05，95%置信区间[CI]：1.03-1.07， FDR < 0.001；甲状腺毒症：OR：1.05，95% CI：1.02-1.08， FDR = 0.016；弥漫性甲状腺肿性甲状腺毒症：OR：1.04，95% CI：1.02-1.07， FDR = 0.003；其他和/或未指定的甲状腺毒症：OR：1.05，95% CI：1.02-1.09， FDR = 0.003），而甲状腺毒症与髋关节 OA 无关。在反向 MR 分析中，OA 的遗传易感性与甲状腺毒症无关。MR 分析中未发现 pleiotropy。敏感性分析表明 MR 估计值具有稳健性。
本研究提供了 MR 证据，支持甲状腺毒症与欧洲人群膝关节 OA 之间存在因果关系，而 OA 可能对甲状腺毒症没有因果影响。
