William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Thyroid. 2023 Dec;33(12):1476-1482. doi: 10.1089/thy.2023.0272. Epub 2023 Oct 26.
Increased height has been associated with increased risk of hypothyroidism or thyroid cancer in epidemiological studies. However, the potential causal association between height and hypothyroidism or thyroid cancer has not been thoroughly explored. Autoimmune thyroid disease (AITD) mainly presents as hypothyroidism, thus we aim to evaluate the causal relationship between height as exposure and its association with AITD or thyroid cancer. Mendelian randomization (MR) analyses were performed by using genetic instruments associated with height, which were selected from the largest genome-wide association meta-analysis for height in up to 5.4 million individuals. Summary-level data for AITD and thyroid cancer (including 30,234 and 3001 cases, respectively) were collected from the large number of available genome-wide association studies. Bidirectional MR was performed to test for reverse causal association between AITD and adult height. MR analyses showed that increased genetically predicted height was associated with a 4% increased risk of AITD ([CI 1.02 to 1.07], -value = 1.99E-03) per 1-standard deviation (SD) increase in genetically predicted height. The bidirectional MR did not show any causal association between AITD and adult height. Additionally, increased genetically predicted height was associated with 15% increased risk of thyroid cancer ([CI 1.07 to 1.23], -value = 2.32E-04) per 1-SD increase in height. Sensitivity analysis confirmed the main results. This MR study showed that 1-SD increase in genetically predicted height was associated with increased risk of AITD and thyroid cancer. In contrast, there was no evidence of a causal association of genetically predicted AITD with height. These results could further aid in investigation of height-related pathways as a means of gaining new mechanistic insights into AITD and thyroid cancer.
在流行病学研究中，身高增加与甲状腺功能减退症或甲状腺癌的风险增加有关。然而，身高与甲状腺功能减退症或甲状腺癌之间的潜在因果关系尚未得到充分探讨。自身免疫性甲状腺疾病（AITD）主要表现为甲状腺功能减退症，因此我们旨在评估身高作为暴露因素与 AITD 或甲状腺癌之间的因果关系。 我们通过使用与身高相关的遗传工具进行孟德尔随机化（MR）分析，这些遗传工具是从多达 540 万人的最大身高全基因组关联荟萃分析中选择的。AITD 和甲状腺癌的汇总水平数据（分别包括 30234 例和 3001 例）是从大量可用的全基因组关联研究中收集的。进行双向 MR 以检验 AITD 和成人身高之间的反向因果关系。 MR 分析表明，与身高相关的遗传预测身高每增加 1 个标准差（SD），AITD 的风险增加 4%（[CI 1.02 至 1.07]，-值=1.99E-03）。双向 MR 没有显示 AITD 和成人身高之间存在任何因果关系。此外，与身高相关的遗传预测身高每增加 1 个 SD，甲状腺癌的风险增加 15%（[CI 1.07 至 1.23]，-值=2.32E-04）。敏感性分析证实了主要结果。 这项 MR 研究表明，与身高相关的遗传预测身高每增加 1 个 SD，AITD 和甲状腺癌的风险就会增加。相比之下，没有证据表明遗传预测的 AITD 与身高之间存在因果关系。这些结果可能有助于进一步研究与身高相关的途径，以获得对 AITD 和甲状腺癌的新机制见解。
