Departement of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden.
J Autoimmun. 2024 Sep;148:103294. doi: 10.1016/j.jaut.2024.103294. Epub 2024 Jul 30.
While multiple sclerosis (MS) affects less than 1 % of the general population, immune mediated inflammatory diseases (IMIDs) collectively influence 5-10 % of the population. Understanding familial co-aggregation of MS and other IMIDs carries important clinical and public health implications that will enable early detection and personalized treatment.
To estimate the familial association between MS and other IMIDs and to quantify their shared genetic basis.
Register-based multi-generational nested case-control familial co-aggregation study and genetic correlation study.
Sweden.
24,995 individuals with MS matched with 253,870 controls and 1,283,502 first-degree relatives (mothers, fathers, full siblings, and offspring) for familial co-aggregation analysis; population of European ancestry for genetic correlation analysis.
Logistic regressions with adjustment for covariates were used to estimate the odds ratios (ORs) of developing MS in individuals with first-degree relatives diagnosed with IMIDs compared to those without such family history. Pairwise genome-wide genetic correlations were estimated with linkage-disequilibrium score regression.
We observed an OR for familial co-aggregation of MS of 1.09 (95 % confidence interval (95%CI) = 1.07-1.11) in families with IMIDs history compared to families without. The association remained broadly consistent after stratification by sex concordance of relative pairs and by kinships. 18 IMID subtypes showed a familial association with MS, 7 of which including other acute widespread myelin destruction, encephalitis or myelitis or encephalomyelitis, inflammatory bowel disease, autoimmune thyroid diseases, systemic lupus erythematosus, other inflammatory system diseases, and sarcoidosis withstood multiple correction. Genetic correlations further revealed a shared genetic basis between 7 IMID subtypes with MS.
We demonstrated a modest familial co-aggregation of MS with several IMIDs, and such association is likely due to shared genetic factors.
多发性硬化症（MS）的发病率低于总人口的 1%，而免疫介导的炎症性疾病（IMIDs）总的来说影响着 5-10%的人口。了解 MS 与其他 IMIDs 的家族聚集性具有重要的临床和公共卫生意义，这将能够实现早期检测和个性化治疗。
评估 MS 与其他 IMIDs 之间的家族关联性，并量化它们的共同遗传基础。
基于登记的多代嵌套病例对照家族聚集性研究和遗传相关性研究。
瑞典。
24995 名 MS 患者与 253870 名对照者以及 1283502 名一级亲属（母亲、父亲、全同胞和子女）进行家族聚集性分析；对具有欧洲血统的人群进行遗传相关性分析。
使用调整协变量的逻辑回归来估计与无家族史者相比，一级亲属患有 IMIDs 的个体患 MS 的比值比（OR）。使用连锁不平衡评分回归估计两两全基因组遗传相关性。
我们观察到，与无家族史者相比，有 IMIDs 家族史的家族中 MS 的家族聚集性 OR 为 1.09（95%置信区间[95%CI]：1.07-1.11）。在按相对对性别一致性和亲属关系分层后，这种关联仍然基本一致。18 种 IMID 亚型与 MS 存在家族关联性，其中 7 种亚型包括其他急性广泛髓鞘破坏、脑炎或脊髓炎或脑脊髓炎、炎症性肠病、自身免疫性甲状腺疾病、系统性红斑狼疮、其他炎症系统疾病和结节病，经多重校正后仍具有统计学意义。遗传相关性进一步表明，7 种与 MS 相关的 IMID 亚型之间存在共同的遗传基础。
我们证明了 MS 与几种 IMIDs 之间存在适度的家族聚集性，这种关联可能是由于共同的遗传因素所致。
