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On the origin of rheumatoid arthritis: the impact of environment and genes--a population based twin study.

Svendsen AJ, Kyvik KO, Houen G, Junker P, Christensen K, Christiansen L, Nielsen C, Skytthe A, Hjelmborg JV - PLoS ONE (2013)

Bottom Line: The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins.Twelve percent (95% CI 0-76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0-72%) to shared environmental effects and 38% (95% CI 17-61%) to non-shared environmental effects.Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant.

View Article: PubMed Central - PubMed

Affiliation: Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. asvendsen@health.sdu.dk

ABSTRACT

Background: Rheumatoid arthritis (RA) is an autoimmune disease with a complex origin. Previous studies have reported heritability estimates on RA at about 60%. Only 16% of the genetic background of the disease has been disclosed so far. The purpose of the present investigation was to provide an optimized estimate on the heritability of RA and to study the recurrence risk in a nationwide Caucasian twin population.

Methods and findings: In a mail survey addressed to 56.707 twin individuals, RA was reported by 479 individuals, mean age 52 (range 16-73). Respondents underwent an interview and clinical examination. Ascertainment probability was 80%. RA was confirmed in 162 twin individuals yielding a prevalence at 0.37% (95% CI 0.31-0.43). The mean discordance time was 19 years (range 0-57). The concordance was 9.1% (95% CI 1.9 to 24.3) in MZ, 6.4% (95% CI 2.1 to 14.3) in DZss. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins. The correlation coefficients were 0.60 (0.33 to 0.78) in monozygotic (MZ) and 0.55 (0.33 to 0.72) in dizygotic same sexed (DZss) pairs. Twelve percent (95% CI 0-76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0-72%) to shared environmental effects and 38% (95% CI 17-61%) to non-shared environmental effects.

Conclusions: This study emphasizes that family factors are important for the development of RA. Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant. However, it should be borne in mind that the genetic and non-genetic components may not be the same across disease subsets.

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Discordance time (years) in RA affected twin pairs according to zygosity.MZ denotes monozygotic, DZss dizygotic same sexed, and DZos dizygotic opposite sexed. From the bottom up the smallest observation, lower, median, upper quartile, and the largest observation is shown. There is one outlier among the DZos pairs.
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pone-0057304-g001: Discordance time (years) in RA affected twin pairs according to zygosity.MZ denotes monozygotic, DZss dizygotic same sexed, and DZos dizygotic opposite sexed. From the bottom up the smallest observation, lower, median, upper quartile, and the largest observation is shown. There is one outlier among the DZos pairs.

Mentions: The box plot shows the distribution of discordance time in each zygosity group (Fig. 1). There was no difference in mean discordance time between any of the zygosity groups. The point prevalence of RA was 0.20% (95% CI 0.14% –0.27%) in men, 0.54% (95% CI 0.44% –0.64%) in women and 0.37% (95% CI 0.31% –0.43%) in men and women, age- and sex adjusted to the 2004 Danish population. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6–35.4 in MZ twins and 17.3–31.6 in DZss twins.


On the origin of rheumatoid arthritis: the impact of environment and genes--a population based twin study.

Svendsen AJ, Kyvik KO, Houen G, Junker P, Christensen K, Christiansen L, Nielsen C, Skytthe A, Hjelmborg JV - PLoS ONE (2013)

Discordance time (years) in RA affected twin pairs according to zygosity.MZ denotes monozygotic, DZss dizygotic same sexed, and DZos dizygotic opposite sexed. From the bottom up the smallest observation, lower, median, upper quartile, and the largest observation is shown. There is one outlier among the DZos pairs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585362&req=5

pone-0057304-g001: Discordance time (years) in RA affected twin pairs according to zygosity.MZ denotes monozygotic, DZss dizygotic same sexed, and DZos dizygotic opposite sexed. From the bottom up the smallest observation, lower, median, upper quartile, and the largest observation is shown. There is one outlier among the DZos pairs.
Mentions: The box plot shows the distribution of discordance time in each zygosity group (Fig. 1). There was no difference in mean discordance time between any of the zygosity groups. The point prevalence of RA was 0.20% (95% CI 0.14% –0.27%) in men, 0.54% (95% CI 0.44% –0.64%) in women and 0.37% (95% CI 0.31% –0.43%) in men and women, age- and sex adjusted to the 2004 Danish population. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6–35.4 in MZ twins and 17.3–31.6 in DZss twins.

Bottom Line: The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins.Twelve percent (95% CI 0-76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0-72%) to shared environmental effects and 38% (95% CI 17-61%) to non-shared environmental effects.Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant.

View Article: PubMed Central - PubMed

Affiliation: Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. asvendsen@health.sdu.dk

ABSTRACT

Background: Rheumatoid arthritis (RA) is an autoimmune disease with a complex origin. Previous studies have reported heritability estimates on RA at about 60%. Only 16% of the genetic background of the disease has been disclosed so far. The purpose of the present investigation was to provide an optimized estimate on the heritability of RA and to study the recurrence risk in a nationwide Caucasian twin population.

Methods and findings: In a mail survey addressed to 56.707 twin individuals, RA was reported by 479 individuals, mean age 52 (range 16-73). Respondents underwent an interview and clinical examination. Ascertainment probability was 80%. RA was confirmed in 162 twin individuals yielding a prevalence at 0.37% (95% CI 0.31-0.43). The mean discordance time was 19 years (range 0-57). The concordance was 9.1% (95% CI 1.9 to 24.3) in MZ, 6.4% (95% CI 2.1 to 14.3) in DZss. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins. The correlation coefficients were 0.60 (0.33 to 0.78) in monozygotic (MZ) and 0.55 (0.33 to 0.72) in dizygotic same sexed (DZss) pairs. Twelve percent (95% CI 0-76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0-72%) to shared environmental effects and 38% (95% CI 17-61%) to non-shared environmental effects.

Conclusions: This study emphasizes that family factors are important for the development of RA. Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant. However, it should be borne in mind that the genetic and non-genetic components may not be the same across disease subsets.

Show MeSH
Related in: MedlinePlus