Geng Chaofan, Tang Yi
Department of Neurology and Innovation Center for Neurological Disorders, Xuanwu Hospital, National Center for Neurological Disorders, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
Acta Neurol Belg. 2024 Dec;124(6):1913-1922. doi: 10.1007/s13760-024-02613-x. Epub 2024 Jul 29.
This research aimed to examine the causal connections between multiple sclerosis (MS) and a range of sex hormone-related traits, such as bioavailable testosterone (BT), sex hormone-binding globulin (SHBG), testosterone, and estradiol (E2).
A bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) was conducted to investigate the relationship between sex hormone-related traits and MS. Moreover, the Inverse-variance weighted (IVW) method was employed as the primary analysis approach.
The MR analysis, using the IVW method, found a significant correlation between genetically determined SHBG levels and MS (OR = 1.634, 95% CI: 1.029-2.599, p = 0.038). Similarly, the reverse MR analysis suggested a causal link between MS and SHBG (OR = 1.005, 95% CI: 1.001-1.009, P = 0.003). However, no association was observed between MS risk and E2, testosterone, or BT levels.
Our MR analysis demonstrated that genetically predicted higher SHBG may be positively correlated with the risk of MS. Moreover, the role of SHBG in MS could be further investigated.
本研究旨在探讨多发性硬化症(MS)与一系列性激素相关特征之间的因果关系,如生物可利用睾酮(BT)、性激素结合球蛋白(SHBG)、睾酮和雌二醇(E2)。
使用全基因组关联研究(GWAS)的汇总统计数据进行双向两样本孟德尔随机化(MR)分析,以研究性激素相关特征与MS之间的关系。此外,采用逆方差加权(IVW)方法作为主要分析方法。
使用IVW方法的MR分析发现,基因决定的SHBG水平与MS之间存在显著相关性(OR = 1.634,95%CI:1.029 - 2.599,p = 0.038)。同样,反向MR分析表明MS与SHBG之间存在因果关系(OR = 1.005,95%CI:1.001 - 1.009,P = 0.003)。然而,未观察到MS风险与E2、睾酮或BT水平之间存在关联。
我们的MR分析表明,基因预测的较高SHBG可能与MS风险呈正相关。此外,SHBG在MS中的作用值得进一步研究。