国家神经系统疾病临床医学研究中心数据管理与共享系统

Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases

Thyroid function in causal relation to MRI markers of cerebral small vessel disease: a Mendelian randomization analysis

第一作者:Yu Tian

通讯作者:Yilong Wang

cerebral small vessel disease; free thyroxine; thyroid function; thyrotropin; white matter integrity

基本信息

  • 负责人:Yu Tian
  • 数据来源: OTHERS
  • 论文编号:OTHERS20230072
  • 发表时间:2023-03-07

2023-03-07

已发表文章

发表杂志:J Clin Endocrinol Metab

发表类型: Original Contributions

影响因子(IF): 6.134

PMID: 36881925 Pubmed原文链接 全文下载

主要研究背景及目的

Observational studies provided insufficient information on the association between thyroid function and the risk of cerebral small vessel disease (CSVD); moreover, the causality of this link was unclear. This study aimed to investigate whether genetically predicted variation within thyroid function was causally associated with the risk of CSVD using two-sample Mendelian randomization (MR) analysis.

方法

In this two-sample MR study with genome-wide association variants, we estimated the causal effects of genetically predicted thyrotropin (TSH; N = 54,288), free thyroxine (FT4; N = 49,269), hypo (N = 51,823), and hyperthyroidism (N = 51,823) on three neuroimaging markers of CSVD, including white matter hyperintensities (WMH; N= 42,310), mean diffusivity (MD; N = 17,467), and fractional anisotropy (FA, N = 17,663). The primary analysis used inverse-variance-weighted MR method, followed by sensitivity analyses using MR-PRESSO, MR-Egger, weighted median, and weighted mode methods.

结论

This study indicated that genetically predicted increased TSH was associated with increased MD, as well as increased FT4 with increased FA, implying the causal effect of thyroid dysfunction on white matter microstructural damages. There was no evidence for causal relationships of hypo or hyperthyroidism with CSVD. Further investigations should verify these findings and clarify the underlying pathophysiological mechanisms.

主要结果

Genetically increased TSH was associated with increased MD (β = 0.311, 95% CI = [0.0763, 0.548], P = 0.01). Genetically increased FT4 was associated with increased FA (β = 0.540, 95% CI = [0.222, 0.858], P < 0.001). Sensitivity analyses using different MR methods showed similar directions but lower precision. No significant associations of hypo and hyperthyroidism with WMH, MD, or FA were found (all P > 0.05).