A genome-wide association study identifies novel susceptibility loci in chronic Chagas cardiomyopathy

CASARES-MARFIL DESIRÉ; STRAUSS MARIANA; BOSCH-NICOLAU PAU; LO PRESTI MARÍA SILVINA; MOLINA ISRAEL; CHEVILLARD CHRISTOPHE; CUNHA-NETO EDECIO; SABINO ESTER; RIBEIRO ANTONIO LUIS; GONZÁLEZ CLARA ISABEL; MARTÍN JAVIER; ACOSTA HERRERA MARIALBERT

CLINICAL INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Lugar: Chicago; Año: 2021 vol. 73 p. 672 - 679

1058-4838

Background: Chagas disease (CD) is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy (CCC) development in Chagas disease patients from different Latin American populations.Methods: Three case-control collections from Colombia, Argentina and Bolivia were genotyped to perform a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3,413 Chagas disease samples. To identify the functional impact of the associated variant and its proxies we performed an in silico analysis of this region. Results: The meta-analysis revealed a novel genome-wide statistically significant association with CCC development in rs2458298 (OR=0.90, 95%CI=0.87-0.94, p-value=3.27x10-08), nearby the SAC3D1 gene. In addition, further in silico analyses displayed functional relationships between the associated variant and the SNX15, BAFT2 and FERMT3 genes, related to cardiovascular traits. Conclusions: Our findings support the role of the host genetic factors in the susceptibility to the development of the chronic cardiac form of this neglected disease.