Background/Purpose: Systemic lupus erythematosus (SLE) is influenced by both genetic and environmental factors. Twin studies in SLE have shown varying levels of concordance. This study aims to further investigate the genetic contribution to SLE by examining the concordance rates among twins from the population-based California Twin Program (CTP), a registry of over 50,000 twins born in California between 1900 and 1982.

Methods: We restricted the data to 13,344 twin pairs with the following inclusion criteria: (1) both completed and returned a baseline screening questionnaire (2) both reported the same zygosity (3) both reported the same sex for each other (4) both were at least 18 years of age when the questionnaire was completed. SLE was determined by self-report or proxy-reported by the co-twin. We compared concordance rates for SLE between MZ and DZ twins, stratified by sex of the twin pairs. Fisher’s exact test was used for the categorical variables and Welch’s two-sample t-test for continuous variables. We also calculated the percent pairwise concordance estimating the probability of both twins having SLE given that SLE has occurred in at least one twin.

Results: The mean age at questionnaire completion for the overall sample of 13,344 eligible twin pairs (39% MZ and 35% like-sex DZ) was 42.3 ± 13.1 years, with 45% female-female pairs, 29% male-male pairs, and 26% male-female pairs, and the following distribution: 80% non-Hispanic white (NHW), 7% Hispanic, 2% Asian and 2% Black. Of these, 99 twin-pairs (30 MZ and 69 DZ), with a mean age of 44.4 ± 9.9 years indicated that at least one twin had SLE and with a substantial level of agreement (i.e., Cohen’s kappa (95% CI): 0.64 (0.56-0.73)) between self-report and cotwin’s proxy report and had similar racial distribution to the overall sample (Table 1).

 Of these 99 twin pairs, six pairs were concordant (three MZ and three DZ) for SLE. The concordance rate was 2.3 times higher in MZ than in DZ twin pairs (with pairwise concordance rates of 10% for MZ and 4.3% for DZ twins, Fisher’s P=0.36). Within MZ twins, female-female pairs had an 11.1% concordance rate, while no concordance was observed in male-male pairs (P=1.0). DZ concordance rates were 1.3 times higher for same-sex pairs compared to male-female pairs (4.8% vs. 3.7%). Among same-sex DZ twins, female-female pairs showed a 5.1% concordance rate (P=1.0) (Table 1).

Conclusion: Higher pairwise concordance rates in MZ twins relative to DZ twins (concordance rate ratio ~ 2.3), and higher rates among female pairs relative to male pairs (11.1% vs 0% for MZ and 5.1% vs 0% in DZ), suggest at least a partial genetic basis and/or early childhood influence for SLE, corroborating previous studies. The limitations include the use of self-reported data and the inclusion of predominantly White patients; thus, our findings cannot be generalizable to other populations. Leveraging the same registry, we plan to explore lifestyle, reproductive, genetic, and other characteristics associated with disease discordance in twin pairs with SLE, which can contribute valuable insights into the pathogenesis of SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-contributions-to-systemic-lupus-erythematosus-concordance-rates-in-california-twins/