Dataset Information

Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study.

ABSTRACT:

Objective

The aim was to estimate familial relative risk (RR) for RA and other autoimmune diseases and the genetic contribution to RA phenotypic variance (heritability).

Methods

This study used the Taiwan National Health Insurance Research Database to identify all National Health Insurance registered beneficiaries (n = 23 658 577) in 2010; among them, 37 482 individuals had RA. We estimated familial RRs and 95% CIs of RA and other autoimmune diseases using marginal Cox proportional models and heritability of RA using a threshold liability model.

Results

The RR (95% CI) for RA was 328.27 (135.95, 795.63) for twins of RA patients; 11.97 (8.68, 16.52) for siblings; 4.86 (4.16, 5.67) for parents; 4.65 (3.92, 5.50) for offspring; and 2.32 (1.83, 2.95) for spouses. Using a threshold liability model, we estimated that familial transmission was 59.4% (95% CI: 50.3, 69.5%) and that heritability was 43.5% (33.9, 54.1%). The RR (95% CI) in individuals with a first-degree relative with RA was 2.91 (2.49, 3.42) for SLE; 2.92 (1.62, 5.25) for SSc; 3.13 (2.50, 3.93) for primary SS; 0.95 (0.36, 2.51) for idiopathic inflammatory myositis; 1.96 (1.54, 2.48) for type 1 diabetes mellitus; 3.32 (1.82, 5.95) for multiple sclerosis; 1.31 (1.31, 2.43) for IBD; 2.76 (2.46, 3.10) for AS; and 1.65 (1.54, 1.77) for psoriasis.

Conclusion

The risks of RA and other autoimmune diseases increased in individuals with an RA family history. Approximately two-thirds of RA phenotypic variation is explained by familial factors.

SUBMITTER: Kuo CF

PROVIDER: S-EPMC5850742 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study.

Kuo Chang-Fu CF Grainge Matthew J MJ Valdes Ana M AM See Lai-Chu LC Yu Kuang-Hui KH Shaw S W Steven SWS Luo Shue-Fen SF Zhang Weiya W Doherty Michael M

Rheumatology (Oxford, England) 20170601 6

<h4>Objective</h4>The aim was to estimate familial relative risk (RR) for RA and other autoimmune diseases and the genetic contribution to RA phenotypic variance (heritability).<h4>Methods</h4>This study used the Taiwan National Health Insurance Research Database to identify all National Health Insurance registered beneficiaries (n = 23 658 577) in 2010; among them, 37 482 individuals had RA. We estimated familial RRs and 95% CIs of RA and other autoimmune diseases using marginal Cox proportiona ...[more]

PMID: 28160009

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Project description:Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease.Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register.Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk.Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.

Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) has been associated with several autoimmune diseases (AD), both within individuals and across relatives, implying common underlying genetic or environmental factors in line with studies indicating that immunological mechanisms are key to brain development. To further elucidate the relationship between ADHD and autoimmunity we performed a population-wide familial co-aggregation study.MethodsWe linked Swedish national registries, defined a birth cohort with their biological relatives and identified individuals diagnosed with ADHD and/or 13 ADs. The cohort included 5 178 225 individuals born between 1960 and 2010, of whom 118 927 (2.30%) had been diagnosed with ADHD. We then investigated the associations between ADHD and ADs within individuals and across relatives, with logistic regression and structural equation modelling.ResultsWithin individuals, ADHD was associated with a diagnosis of any of the 13 investigated ADs (adjusted odds ratio (OR) =1.34, 95% confidence interval (CI) = 1.30-1.38) as well as several specific ADs. Familial co-aggregation was observed. For example, ADHD was associated with any of the 13 ADs in mothers (OR = 1.29, 95% CI = 1.26-1.32), fathers (OR = 1.14, 95% CI = 1.11-1.18), full siblings (OR = 1.19, 95% CI = 1.15-1.22), aunts (OR = 1.12, 95% CI = 1.10-1.15), uncles (OR = 1.07, 95% CI = 1.05-1.10) and cousins (OR = 1.04, 95% CI = 1.03-1.06). Still, the absolute risks of AD among those with ADHD were low. The genetic correlation between ADHD and a diagnosis of any of the investigated ADs was 0.13 (95% CI = 0.09-0.17) and the environmental correlation was 0.02 (95% CI = -0.03-0.06).ConclusionsWe found that ADHD and ADs co-aggregate among biological relatives, indicating that the relationship between ADHD and autoimmune diseases may in part be explained by shared genetic risk factors. The patterns of familial co-aggregation of ADHD and ADs do not readily support a role of maternal immune activation in the aetiology of ADHD. The findings have implications for aetiological models of ADHD. However, screening for autoimmunity among individuals with ADHD is not warranted.

Dataset Information

Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study.

Objective

Methods

Results

Conclusion

Publications

Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: a nationwide population-based study.

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