Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Mult Scler. 2023 Sep;29(10):1209-1215. doi: 10.1177/13524585231185258. Epub 2023 Jul 12.
The two main phenotypes of multiple sclerosis (MS), primary progressive (PPMS) and relapsing Onset (ROMS), show clinical and demographic differences suggesting possible differential risk mechanisms. Understanding the heritable features of these phenotypes could provide aetiological insight.
To evaluate the magnitude of familial components in PPMS and ROMS and to estimate the heritability of disease phenotypes.
We used data from 25,186 MS patients of Nordic ancestry from the Swedish MS Registry between 1987 and 2019 with known disease phenotype (1593 PPMS and 16,718 ROMS) and 251,881 matched population-based controls and 3,364,646 relatives of cases and controls. Heritability was calculated using threshold-liability models. For familial odds ratios (ORs), logistic regression with robust sandwich estimator was utilized.
The OR of MS diagnosis in those with a first-degree family member with ROMS was 7.00 and 8.06 in those with PPMS. The corresponding ORs for having a second-degree family member with ROMS was 2.16 and 2.18 in PPMS. The additive genetic effect in ROMS was 0.54 and 0.22 in PPMS.
Risk of MS increases by several folds in those with a relative with MS. The likelihood of developing either disease phenotype appears independent of genetic predisposition.
多发性硬化症（MS）的两种主要表型，原发性进展型（PPMS）和复发性发病型（ROMS），表现出临床和人口统计学差异，表明可能存在不同的风险机制。了解这些表型的遗传特征可以提供病因学的见解。
评估 PPMS 和 ROMS 中家族成分的大小，并估计疾病表型的遗传性。
我们使用了来自瑞典多发性硬化症登记处 1987 年至 2019 年间的北欧血统的 25186 名 MS 患者的数据，这些患者已知疾病表型（1593 名 PPMS 和 16718 名 ROMS），并与 251881 名基于人群的对照和 3364646 名病例和对照的亲属进行了匹配。使用阈限 Liability 模型计算遗传度。对于家族优势比（OR），使用稳健的 sandwich 估计量进行逻辑回归。
有 ROMS 一级亲属的 MS 诊断的 OR 为 7.00，有 PPMS 一级亲属的 OR 为 8.06。有 ROMS 二级亲属的 OR 分别为 2.16 和 2.18。在 ROMS 中，加性遗传效应为 0.54，在 PPMS 中为 0.22。
有亲属患有 MS 的人患 MS 的风险增加了数倍。发展任何一种疾病表型的可能性似乎与遗传易感性无关。
