A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy.
Trypanosoma cruzi
Chagas disease
GWAS
Latin American
cardiomyopathy
genetic association
meta-analysis
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
received:
04
12
2020
accepted:
01
02
2021
pubmed:
5
2
2021
medline:
23
9
2021
entrez:
4
2
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33539531
pii: 6128793
doi: 10.1093/cid/ciab090
pmc: PMC8366831
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
672-679Subventions
Organisme : NHLBI NIH HHS
ID : HHSN268200417175C
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI098461
Pays : United States
Organisme : Red Iberoamericana de medicina genómica en enfermedad de Chagas
ID : RIMGECH-217RT0524
Organisme : CYTED
Organisme : Ministerio de Ciencia y Tecnología de Córdoba
ID : PID 2018
Organisme : Secretaría de Ciencia y Tecnología
ID : 2018-2021
Organisme : NIAID NIH HHS
ID : P50 AI098461
Pays : United States
Organisme : CNPq
ID : 310679/2016-8
Organisme : FAPEMIG
ID : PPM-00428-17
Organisme : NHLBI NIH HHS
Pays : United States
Organisme : Agence Nationale de Recherche
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.