A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy

Desiré Casares-Marfil (1) , Mariana Strauss (2) , Pau Bosch-Nicolau , María Silvina Lo Presti (2) , Israel Molina , Christophe Chevillard (3) , Edecio Cunha-Neto (4) , Ester Sabino (4) , Antonio Luiz P Ribeiro (5) , Clara Isabel González (6) , Javier Martín (1) , Marialbert Acosta-Herrera (1)

1 IPBLN-CSIC - Instituto de Parasitología y Biomedicina López-Neyra
2 Universidad Nacional de Córdoba [Argentina]
3 TAGC - Theories and Approaches of Genomic Complexity
4 USP - Universidade de São Paulo = University of São Paulo
5 UFMG - Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil]
6 UIS - Universidad Industrial de Santander [Bucaramanga]

Background Chagas disease 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 development in Chagas disease patients from different Latin American populations. Methods We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia. Samples were genotyped to conduct a genome-wide association study (GWAS). These results were meta-analyzed with summary statistic data from Brazil, gathering a total of 3413 Chagas disease patients. 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 chronic Chagas cardiomyopathy development in rs2458298 (OR = 0.90, 95%CI = 0.87–0.94, P-value = 3.27 × 10-08), 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.

Mots clés: Chagas disease; cardiomyopathy; genetic association; GWAS; Latin American; meta-analysis; Trypanosoma cruzi

Domaines: Maladies infectieuses; Cardiologie et système cardiovasculaire; Génétique humaine; Génétique des populations [q-bio.PE]

Desiré Casares-Marfil, Mariana Strauss, Pau Bosch-Nicolau, María Silvina Lo Presti, Israel Molina, et al.. A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy. Clinical Infectious Diseases, 2021, 73 (4), pp.672-679. ⟨10.1093/cid/ciab090⟩. ⟨hal-03249865⟩