Genetic and environmental mediators of multiple sclerosis susceptibility but not early severity run in families

IF 2.9 3区医学 Q2 CLINICAL NEUROLOGY

Multiple sclerosis and related disorders Pub Date : 2026-05-01 Epub Date: 2026-02-28 DOI:10.1016/j.msard.2026.107101

Cato E.A. Corsten , Ana M. Marques , Yifan van Hasselt , Jeroen van Rooij , Ide Smets , Marvin M. van Luijn , Rinze F. Neuteboom , Beatrijs Wokke , Joost Smolders

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引用次数: 0

Abstract

Background

Multiple sclerosis (MS) susceptibility and severity are mediated by different genetic and environmental risk factors. Familial aggregation in MS is partially explained by susceptibility determinants, yet impact on early disease course after clinically isolated syndrome (CIS) is uncertain. We investigated associations of reported familial MS with genetic and environmental risk factors, and with clinical presentation and disease course after CIS.

Methods

CIS participants were included in a prospective cohort within six months after symptom onset. Family history was assessed at baseline. We evaluated weighted genetic risk scores (wGRS) for MS susceptibility, 25-hydroxyvitamin D (25(OH)D) and body mass index (BMI), and determined HLA-DRB1*15:01 and MS severity SNP rs10191329 carriership. Anti-Epstein Barr virus Nuclear Antigen-1 (anti-EBNA1) IgG antibodies and 25(OH)D levels were measured. Disease course associations were estimated with Cox regression.

Results

Family members with MS were reported by 81/415 (19.5%) CIS participants. Familial MS was associated with higher MS susceptibility wGRS (7.54 (SD1.17) vs. 7.19 (SD1.22), p=0.04) and more frequent HLA-DRB1*15:01 carriership (first-degree 66.7%, other-degree 30.2%, no 38.4%, p=0.02). Anti-EBNA1 IgG and 25(OH)D levels did not differ, yet wGRS for lower 25(OH)D and higher adult BMI characterised MS participants with first-degree MS relatives. Baseline characteristics and disease severity measures were similar between participants with and without familial MS.

Conclusion

Our results confirm that familial MS is associated with enrichment of genetic risk for MS susceptibility, low 25(OH)D and high BMI, but not with early disease course after CIS. These data support that MS susceptibility and disease course are driven by different pathophysiological processes.

查看原文本刊更多论文

多发性硬化症易感性的遗传和环境介质，但不是早期严重程度在家庭中运行。

背景：多发性硬化症（MS）的易感性和严重程度是由不同的遗传和环境危险因素介导的。多发性硬化症的家族聚集性可以部分解释为易感性决定因素，但对临床孤立综合征（CIS）后早期病程的影响尚不确定。我们调查了已报道的家族性MS与遗传和环境危险因素的关系，以及与CIS后的临床表现和病程的关系。方法：CIS参与者在症状出现后6个月内纳入前瞻性队列。基线时评估家族史。我们评估了MS易感性、25-羟基维生素D （25(OH)D）和体重指数（BMI）的加权遗传风险评分（wGRS），并确定了HLA-DRB1*15:01和MS严重程度SNP rs10191329携带者。检测抗eb病毒核抗原1 (ebna1) IgG抗体和25(OH)D水平。用Cox回归估计病程相关性。结果：81/415 (19.5%)CIS参与者报告有MS家庭成员。家族性MS易感性wGRS较高(7.54 (SD1.17) vs. 7.19 (SD1.22), p=0.04)， HLA-DRB1*15:01携带频率较高（一级66.7%，其他级30.2%，非一级38.4%,p=0.02）。抗ebna1 IgG和25(OH)D水平没有差异，但25(OH)D较低和成人BMI较高的wGRS特征是有一级MS亲属的MS参与者。结论：我们的研究结果证实，家族性MS与MS易感性遗传风险的增加、低25(OH)D和高BMI相关，但与CIS后的早期病程无关。这些数据支持MS易感性和病程是由不同的病理生理过程驱动的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Multiple sclerosis and related disorders CLINICAL NEUROLOGY-

CiteScore

5.80

自引率

20.00%

发文量

814

审稿时长

66 days

期刊介绍： Multiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported by key researchers from all neuroscience domains that focus on MS and associated disease of the central nervous system. The primary aim of this new journal is the rapid publication of high quality original research in the field. Important secondary aims will be timely updates and editorials on important scientific and clinical care advances, controversies in the field, and invited opinion articles from current thought leaders on topical issues. One section of the journal will focus on teaching, written to enhance the practice of community and academic neurologists involved in the care of MS patients. Summaries of key articles written for a lay audience will be provided as an on-line resource. A team of four chief editors is supported by leading section editors who will commission and appraise original and review articles concerning: clinical neurology, neuroimaging, neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement scales, teaching, neuroethics and lay communication.