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
2023-03-07
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
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.
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.
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.
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).