Shared aetiology underlying multiple sclerosis and other immune mediated inflammatory diseases: Swedish familial co-aggregation and large-scale genetic correlation analyses

IF 7.9 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2024-07-30 DOI:10.1016/j.jaut.2024.103294

Qianwen Liu , Yuan Jiang , Thomas Frisell , Pernilla Stridh , Klementy Shchetynsky , Lars Alfredsson , Ingrid Kockum , Ali Manouchehrinia , Xia Jiang

{"title":"Shared aetiology underlying multiple sclerosis and other immune mediated inflammatory diseases: Swedish familial co-aggregation and large-scale genetic correlation analyses","authors":"Qianwen Liu , Yuan Jiang , Thomas Frisell , Pernilla Stridh , Klementy Shchetynsky , Lars Alfredsson , Ingrid Kockum , Ali Manouchehrinia , Xia Jiang","doi":"10.1016/j.jaut.2024.103294","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Objective</h3><p>To estimate the familial association between MS and other IMIDs and to quantify their shared genetic basis.</p></div><div><h3>Design</h3><p>Register-based multi-generational nested case-control familial co-aggregation study and genetic correlation study.</p></div><div><h3>Setting</h3><p>Sweden.</p></div><div><h3>Participants</h3><p>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.</p></div><div><h3>Measurements</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>We demonstrated a modest familial co-aggregation of MS with several IMIDs, and such association is likely due to shared genetic factors.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"148 ","pages":"Article 103294"},"PeriodicalIF":7.9000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124001288/pdfft?md5=1f67eefcafd5b7fc808603cea2f02fef&pid=1-s2.0-S0896841124001288-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0896841124001288","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

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.

Objective

To estimate the familial association between MS and other IMIDs and to quantify their shared genetic basis.

Design

Setting

Sweden.

Participants

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.

Measurements

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.

Results

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.

Conclusion

We demonstrated a modest familial co-aggregation of MS with several IMIDs, and such association is likely due to shared genetic factors.

查看原文本刊更多论文

多发性硬化症和其他免疫介导的炎症性疾病的共同病因：瑞典家族聚集和大规模遗传相关性分析。

背景：多发性硬化症（MS）的患病率不到总人口的 1%，而免疫介导的炎症性疾病（IMIDs）的患病率则高达总人口的 5-10%。了解多发性硬化症和其他免疫介导的炎症性疾病的家族聚集性具有重要的临床和公共卫生意义，将有助于早期发现和个性化治疗：估计多发性硬化症和其他综合症之间的家族关联，并量化其共同的遗传基础：设计：基于登记的多代嵌套病例对照家族共同聚集研究和遗传相关性研究：参与者：24,995名多发性硬化症患者与253,870名对照者和1,283,502名一级亲属（母亲、父亲、兄弟姐妹和后代）配对，进行家族共聚分析；欧洲血统人群进行遗传相关性分析：采用调整协变量的逻辑回归来估算有一级亲属被诊断为 IMIDs 的个体与无此类家族史的个体相比患多发性硬化症的几率比（ORs）。用连锁失衡分数回归法估算了配对全基因组遗传相关性：我们观察到，与无 IMIDs 家族史的家族相比，有 IMIDs 家族史的家族共同聚集多发性硬化症的 OR 值为 1.09（95% 置信区间 (95%CI) = 1.07-1.11）。根据亲属配对的性别一致性和亲缘关系进行分层后，这种关联仍基本一致。18种IMID亚型与多发性硬化症存在家族关联，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肉样瘤病）经受住了多重校正。遗传相关性进一步揭示了7种IMID亚型与多发性硬化症之间的共同遗传基础：结论：我们证明了多发性硬化症与几种 IMID 之间存在一定程度的家族聚集性，这种关联很可能是由共同的遗传因素造成的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.