Concordance of autoimmune disease in a nationwide Danish systemic lupus erythematosus twin cohort
Introduction
Systemic lupus erythematosus (SLE) is a chronic, multisystemic autoimmune disease with a heterogeneous disease presentation and a relapsing-remitting clinical course. It is characterized by the production of anti-nuclear autoantibodies, immune complex deposition and inflammatory reaction leading to multi-organ involvement, for example, skin, joints, serosal surfaces, kidneys, and brain [1], [2]. The worldwide prevalence has been estimated to be around 0.02–0.07% [3] and 0.045% in Denmark [4] with a 9:1 female predominance and disease onset typically during childbearing years [5].
SLE is a complex disease with both environmental and genetic effects contributing to disease susceptibility [6], where heritability has been estimated to lie between 44% and 66% [7], [8], [9]. Genome-wide association studies have identified more than 50 SLE-associated genetic risk loci, which approximately account for 27% of the heritability [10], but many factors remain unknown. The classical twin study design may help shed new light on the relative influence of genetic and environmental effects on disease susceptibility and population-based studies may be considered of particular interest as they are less susceptible to selection bias. Only one previous population-based twin study has looked into SLE concordance, which found a pairwise concordance rate of 14.3% among monozygotic (MZ) twins and no concordant dizygotic (DZ) twins [11]. In comparison, pairwise concordance estimates in non-population-based twin studies have varied between 24.4% to 57.1% in MZ twins and 0% to 1.6% in DZ twins [12], [13], [14]. In addition to familial aggregation of SLE, other autoimmune diseases may also cluster within families [8], [15], but previous twin studies have not focused on this aspect of twin concordance.
In the present study, we present population-based concordance rates and prevalence of SLE in twins recruited from the Danish Twin Registry (DTR), as well as co-aggregating autoimmune diseases.
Section snippets
Twins
Using the unique identification number assigned to all Danish residents in the Civil Registration System [16] we identified all living individuals with an SLE diagnosis by record linkage between the Danish Twin Registry (DTR) and the National Patient Register (NPR) [17] using the International Classification of Diseases (ICD) codes M32 (ICD-10) and 73419 (ICD-8). The DTR is a population-based nationwide registry of multiple births in Denmark with an approximately 90% completeness for twin pairs
Record linkage between the NPR and DTR
In January 2014, a total of 75,643 living twin individuals above the age of 20 years were registered in the DTR. Sixty-nine twins had a registered SLE diagnosis in the NPR, corresponding to 13 MZ, 26 same-sex DZ (DZss), 23 opposite-sex DZ (DZos) and three twin pairs of unknown zygosity, as well as one set of triplets and one set of quadruplets, amounting to 137 persons (Fig.). One MZ and one DZss twin pairs were registered as concordant for SLE.
SLE patients
Medical records and telephone interviews confirmed
Discussion
While in recent years genome-wide association studies have identified individual SLE susceptibility loci, twin concordance may still shed new light on the roles of genetic and environmental influences. Ideally, a highly heritable disease should be related to a high MZ twin concordance with similar disease traits, earlier age at diagnosis and lower discordance time between MZ twins. In comparison, there should be a lower concordance among DZ twins, who only share half their segregating genes,
Acknowledgments
Special thanks to Axel Skytthe, the Danish Twin Registry, for his invaluable help with extracting the twin data.
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Cited by (0)
This work was supported by the Danish Rheumatism Association, Denmark (Grant nos. R123-A3159 and R97-A1028); and the A.P. Møller Foundation, Denmark (Grant no. 14-447).