Dados do Trabalho

Title

GENETIC ANCESTRY AND ITS CONTRIBUTION TO COMPLEX TRAITS IN CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

Background

Based on the hypothesis that ancestry influences the susceptibility and development of lupus, this study has evaluated the role of admixture degree in clinical manifestations of childhood-onset systemic lupus erythematosus (cSLE) in a tri-hybrid population.

Materials and methods

The genome-wide human Cytoscan HD array was applied to genotype 2.6K markers in 107 cSLE Brazilian patients and 110 healthy controls. Quality control of the chip was carried out using Chromosome Analysis Suite software. A panel of 345 ancestry informative markers (AIMs) based on SNP data from Cytoscan HD array was used to infer the proportion of European, African and Amerindian ancestries of each cSLE and control subjects. The individual ancestral composition based on the SNP-AIMs set was estimated using Admixture. Statistical analyses to associate the genetic ancestry with different clinical traits were performed using the computing environment R.

Results

Ancestral composition analysis revealed that the main component of patients and control group was European (66.9% and 80.2%), followed by African (21.6% and 11.5%) and Amerindian (11.5% and 8.4%). Comparisons using the proportions of each ancestral component showed significant differences in European (p = 4.7 x 10-11, 95% CI -0.18− -0.10), African (p = 4.1 x 10-9, 95% CI 0.05 − 0.12) and Amerindian (p = 1.9 x 10-6, 95% CI -0.03 − 0.06) ancestries between cSLE and control groups.
A higher proportion of Amerindian ancestry in cSLE was associated to development of photosensitivity (p = 0.035) and hematologic alterations (p = 0.025). Otherwise, a higher African component was protective against hypocomplementemia (p = 0.021).

Conclusions

Results described here show novel associations to clinical manifestations in cSLE according to the ancestry profile. The deeper investigation of its relation to the pathogenesis may contribute to the understanding of the genetic basis of the disease.