دورية أكاديمية
Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature.
| العنوان: | Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature. |
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| المؤلفون: | Sabino EC; Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Laboratório de Parasitologia Médica (LIM-46), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Franco LAM; Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Laboratório de Parasitologia Médica (LIM-46), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Venturini G; Laboratorio de Genetica e Cardiologia Molecular, Instituto do Coracao (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazila.; Genetics Department, Harvard Medical School, Boston, Massachusetts, United States of America., Velho Rodrigues M; Laboratorio de Genetica e Cardiologia Molecular, Instituto do Coracao (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazila., Marques E; Laboratorio de Genetica e Cardiologia Molecular, Instituto do Coracao (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazila., Oliveira-da Silva LC; Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Laboratório de Parasitologia Médica (LIM-46), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Martins LNA; Department of Statistics, Instituto de Ciência Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Ferreira AM; Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Almeida PEC; Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., Silva FDD; Departamento de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.; Laboratório de Parasitologia Médica (LIM-46), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Leite SF; Health Science Program, Universidade Estadual de Montes Claros, Montes Claros, Brazil., Nunes MDCP; Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Haikal DS; Health Science Program, Universidade Estadual de Montes Claros, Montes Claros, Brazil., Oliveira CDL; Federal University of São João del-Rei, Divinópolis, Brazil., Cardoso CS; Federal University of São João del-Rei, Divinópolis, Brazil., Seidman JG; Genetics Department, Harvard Medical School, Boston, Massachusetts, United States of America., Seidman CE; Genetics Department, Harvard Medical School, Boston, Massachusetts, United States of America.; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America., Casas JP; Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.; Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America., Ribeiro ALP; Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Telehealth Center, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Krieger JE; Laboratorio de Genetica e Cardiologia Molecular, Instituto do Coracao (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazila., Pereira AC; Laboratorio de Genetica e Cardiologia Molecular, Instituto do Coracao (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazila.; Genetics Department, Harvard Medical School, Boston, Massachusetts, United States of America. |
| المصدر: | PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2022 Oct 10; Vol. 16 (10), pp. e0010725. Date of Electronic Publication: 2022 Oct 10 (Print Publication: 2022). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
| مواضيع طبية MeSH: | Chagas Cardiomyopathy* , Chagas Disease* , Trypanosoma cruzi*/physiology, Chromatin ; Chromosomes, Human, Pair 18/genetics ; Chromosomes, Human, Pair 18/metabolism ; Genome-Wide Association Study ; Humans |
| مستخلص: | Background: Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/principal Findings: We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10-9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. Conclusions/significance: We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted. Competing Interests: The authors have declared that no competing interests exist. |
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| معلومات مُعتمدة: | United States HHMI Howard Hughes Medical Institute; U19 AI098461 United States AI NIAID NIH HHS; P50 AI098461 United States AI NIAID NIH HHS; U01 AI168383 United States AI NIAID NIH HHS; R01 HL133165 United States HL NHLBI NIH HHS |
| المشرفين على المادة: | 0 (Chromatin) |
| تواريخ الأحداث: | Date Created: 20221010 Date Completed: 20221012 Latest Revision: 20230131 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9550069 |
| DOI: | 10.1371/journal.pntd.0010725 |
| PMID: | 36215317 |
| قاعدة البيانات: | MEDLINE |
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