Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins

AJ MacGregor, H Snieder, AS Rigby… - … : Official Journal of …, 2000 - Wiley Online Library
AJ MacGregor, H Snieder, AS Rigby, M Koskenvuo, J Kaprio, K Aho, AJ Silman
Arthritis & Rheumatism: Official Journal of the American College …, 2000Wiley Online Library
Objective Twin concordance data for rheumatoid arthritis (RA) on their own provide only
limited insight into the relative genetic and environmental contribution to the disease. We
applied quantitative genetic methods to assess the heritability of RA and to examine for
evidence of differences in the genetic contribution according to sex, age, and clinical
disease characteristics. Methods Data were analyzed from 2 previously published
nationwide studies of twins with RA conducted in Finland and the United Kingdom …
Objective
Twin concordance data for rheumatoid arthritis (RA) on their own provide only limited insight into the relative genetic and environmental contribution to the disease. We applied quantitative genetic methods to assess the heritability of RA and to examine for evidence of differences in the genetic contribution according to sex, age, and clinical disease characteristics.
Methods
Data were analyzed from 2 previously published nationwide studies of twins with RA conducted in Finland and the United Kingdom. Heritability was assessed by variance components analysis. Differences in the genetic contribution by sex, age, age at disease onset, and clinical characteristics were examined by stratification. The power of the twin study design to detect these differences was examined through simulation.
Results
The heritability of RA was 65% (95% confidence interval [95% CI] 50–77) in the Finnish data and 53% (95% CI 40–65) in the UK data. There was no significant difference in the strength of the genetic contribution according to sex, age, age at onset, or disease severity subgroup. Both study designs had power to detect a contribution of at least 40% from the common family environment, and a difference in the genetic contribution of at least 50% between subgroups.
Conclusion
Genetic factors have a substantial contribution to RA in the population, accounting for ∼60% of the variation in liability to disease. Although tempered by power considerations, there is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity.
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