Qianwen Liu , Yuan Jiang , Thomas Frisell , Pernilla Stridh , Klementy Shchetynsky , Lars Alfredsson , Ingrid Kockum , Ali Manouchehrinia , Xia Jiang
{"title":"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。","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":"{\"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}","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}
Shared aetiology underlying multiple sclerosis and other immune mediated inflammatory diseases: Swedish familial co-aggregation and large-scale genetic correlation analyses
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
Register-based multi-generational nested case-control familial co-aggregation study and genetic correlation study.
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.
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.
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