Familial Associations of Rheumatoid Arthritis With Autoimmune Diseases and Related Conditions
Familial Associations of Rheumatoid Arthritis With Autoimmune Diseases and Related Conditions
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DOI：
10.1002/art.24328
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发表时间：
2009-03-01
影响因子：
--
通讯作者：
Sundquist, Kristina
中科院分区：
文献类型：
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作者：
Hemminki, Kari;Li, Xinjun;Sundquist, Kristina
Objective.在全基因组关联研究的时代，家族风险被用来估计疾病的遗传性和候选基因识别的可能性。本研究旨在评估类风湿性关节炎（RA）与33种自身免疫性疾病及相关疾病在父母和子女、独生子女、双胞胎和配偶中的关系。在上个世纪，瑞典的多代同堂登记册被用作瑞典家庭信息的可靠来源。个别家庭成员的自身免疫性疾病的数据是通过与医院出院登记册的联系获得的。标准化发病率比（SIR）计算为RA患者或其他33种自身免疫性疾病或相关疾病患者的家庭成员患RA的相对危险度，并与那些没有受累家庭成员的RA相对危险度进行比较。在总共447，704名患者中，有47，361名被诊断为RA。患病父母的后代、同胞、多家系、双生子和配偶的SIRs分别为3.02、4.64、9.31、6.48和1.17。根据父母先证者，强直性脊柱炎与后代RA的家族风险有显著相关性（SIR 2.96），局限性硬皮病（SIR 2.40），干燥综合征（SIR 2.25），系统性红斑狼疮（SIR 2.13），系统性硬化症（SIR 1.65），桥本甲状腺炎/甲状腺功能减退症（SIR 1.54）、恶性贫血（SIR 1.53）、结节病（SIR 1.40）、银屑病（SIR 1.36）、韦格纳肉芽肿病（SIR 1.34）、哮喘或风湿性多肌痛（SIR 1.32）。这是第一项使用来自单一人群的数据比较RA与大量自身免疫性疾病和相关疾病的家族风险的研究。该人群中高不一致的家族风险表明RA和相关疾病之间存在广泛的遗传共享。
Objective. In the era of genome-wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate-gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses.Methods. The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member.Results. Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjogren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1,34), and asthma or polymyalgia rheumatica (SIR 1.32).Conclusion. This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.