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Abstract Number: 1182

Familial Aggregation and Heritability of Rheumatoid Arthritis in Taiwan: A Nationwide Population Study

Chang-Fu Kuo1, Matthew J. Grainge2, Kuang-Hui Yu3, Lai-Chu See4, Shue-Fen Luo3, Ana M. Valdes5, I-Jun Chou6, Hsiao-Chun Chang3, Weiya Zhang1 and Michael Doherty7, 1Academic Rheumatology, School of Clinical Sciences, University of Nottingham, Nottingham, United Kingdom, 2Division of Epidemiology and Public Health, School of Community Health Sciences,, University of Nottingham, Nottingham, United Kingdom, 3Division of Rheumatology, Immunology and Allergy, Chang Gung Memorial Hospital, Taoyuan, Taiwan, 4Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan, 5Dept of Twin Research and Genetic Epidemiology, St. Thomas' Hospital, King's College London, London, United Kingdom, 6Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan, 7Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Family studies and rheumatoid arthritis, pathogenesis

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Session Information

Session Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The present study was to estimate the familial relative risk (RR) of rheumatoid arthritis (RA) in individuals with affected first-degree relatives compared to individuals with no affected first-degree relatives.  We also estimated the heritability to assess the magnitude of genetic contribution to susceptibility to RA.

Methods:

Using data from the National Health Insurance Research Database in Taiwan, we conducted a nationwide cross-sectional study of data collected from 11,449,138 men and 11,800,070 women in 2010. RA cases were those receiving a catastrophic illness certificate for RA. The identification of first-degree relatives of each individual was determined using the NIHRD registry for beneficiaries. This specifies relationships between the insured person who paid the insurance fee and his/her dependents, allowing first-degree relatives (father, mother, son, daughter, brother, sister, twin) to be identified directly. Full siblings were identified as individuals who shared the same parents. Twins were full siblings who shared the same date of birth. The marginal Cox proportional hazard model with an equal follow-up time, adjusting for age and sex, was used to estimate RR (95% confidence interval [95% CI]) of RA in individuals with affected first-degree relatives. This model was used to account for shared environment and case clustering within families with robust variance. Heritability was estimated using multifactorial polygenic model.

Results:

There were 8,010 men (0.07%) and 30,200 women (0.26%) who had RA catastrophic illness certificate in 2010. The prevalence of RA was higher in individuals with affected first-degree relatives (0.51%) than those without (0.16%). The overall familial RR was 4.79 (95% CI, 4.08–5.63). An individual’s risk for RA varied depending on which of their family members were affected. The RRs (95% CIs) for an individual with an affected twin, sibling, offspring and parent were 20.95 (6.59–66.62), 8.93 (5.59–14.27), 4.46 (3.63–5.47) and 4.60 (3.90–5.44), respectively. The RR (95% CI) increased with the number of affected first-degree relatives, from 4.65 (3.95–5.46), 44.46 (18.90–3.09) and 118.34 (13.11–1068.55) for one, two or three or more affected relatives. The heritability of RA was 0.54 (95% CI, 0.42–0.67). 

Conclusion:

This population-based study confirms that RA aggregates within families and the heritability of RA is high. Genetic predisposition contributes to a significant proportion of RA development.


Disclosure:

C. F. Kuo,
None;

M. J. Grainge,
None;

K. H. Yu,
None;

L. C. See,
None;

S. F. Luo,
None;

A. M. Valdes,
None;

I. J. Chou,
None;

H. C. Chang,
None;

W. Zhang,
None;

M. Doherty,
None.

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