Familial Risks and Heritability of Rheumatoid Arthritis Role of Rheumatoid Factor/Anti-Citrullinated Protein Antibody Status, Number and Type of Affected Relatives, Sex, and Age

被引:143
作者
Frisell, Thomas [1 ]
Holmqvist, Marie [1 ]
Kallberg, Henrik [2 ]
Klareskog, Lars [1 ]
Alfredsson, Lars [2 ]
Askling, Johan [1 ]
机构
[1] Karolinska Inst, Solna, Sweden
[2] Karolinska Inst, S-17176 Stockholm, Sweden
来源
ARTHRITIS AND RHEUMATISM | 2013年 / 65卷 / 11期
基金
英国医学研究理事会; 瑞典研究理事会;
关键词
AUTOIMMUNE-DISEASES; ASSOCIATION; NATIONWIDE; POPULATION; GENETICS; COHORT; TWINS; AGGREGATION; INFERENCE; REGISTER;
D O I
10.1002/art.38097
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
ObjectiveTo estimate familial aggregation of rheumatoid arthritis (RA) in 3 large population-representative samples and to test if familial aggregation is affected by rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) status, type of relative, sex, and age at onset of RA. MethodsA register-based nested case-control study was performed in the Swedish total population. Data on patients with RA were ascertained through the nationwide Swedish Patient Register (n = 88,639), the clinical Swedish Rheumatology Quality Register (n = 11,519), and the Epidemiological Investigation of Rheumatoid Arthritis case-control study (n = 2,871). Data on first- and second-degree relatives were obtained through the Swedish Multigeneration Register. Familial risks were calculated using conditional logistic regression. ResultsConsistent across data sources, the familial odds ratio for RA was approximate to 3 in first-degree relatives of RA patients and 2 in second-degree relatives. Familial risks were similar among siblings, parents, and offspring. Familial aggregation was not modified by sex, but was higher in RA patients with early-onset disease and in RF/ACPA-positive RA patients. The observed familial risks were consistent with a heritability of approximate to 50% for ACPA-positive RA and approximate to 20% for ACPA-negative RA. ConclusionThe pattern of risks suggests that familial factors influence RA in men and women equally and that these factors are of less importance for late-onset RA. Familial factors are more important for seropositive RA, but there is significant familial overlap between seropositive RA and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest that heritability of RA is lower than previously reported, in particular for ACPA-negative RA.
引用
收藏
页码:2773 / 2782
页数:10
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