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. |
References: | PLoS Negl Trop Dis. 2018 Dec 5;12(12):e0006998. (PMID: 30517089) Bioinformatics. 2021 Mar 17;:. (PMID: 33734315) Immun Inflamm Dis. 2018 Mar;6(1):47-57. (PMID: 28967229) J Immunol Res. 2022 Jan 20;2022:7070301. (PMID: 35097133) Nat Med. 2021 Apr;27(4):668-676. (PMID: 33837377) Bioinformatics. 2005 Jan 15;21(2):263-5. (PMID: 15297300) PLoS Negl Trop Dis. 2014 Jul 31;8(7):e3010. (PMID: 25077613) PLoS Negl Trop Dis. 2013;7(2):e2078. (PMID: 23469305) Hum Pathol. 2010 Apr;41(4):528-34. (PMID: 20004942) PLoS Genet. 2019 Dec 23;15(12):e1008500. (PMID: 31869403) Front Cell Infect Microbiol. 2021 Sep 06;11:722984. (PMID: 34552885) Scand J Immunol. 2010 Dec;72(6):529-39. (PMID: 21044127) PLoS One. 2013 Nov 20;8(11):e79629. (PMID: 24324551) Front Cell Infect Microbiol. 2021 Nov 17;11:758273. (PMID: 34869064) Eur J Hum Genet. 2016 May;24(5):725-31. (PMID: 26395555) Front Immunol. 2020 Mar 03;11:306. (PMID: 32194558) Nature. 2018 Jun;558(7708):73-79. (PMID: 29875488) J Infect Dis. 2022 May 4;225(9):1601-1610. (PMID: 34623435) Bioinformatics. 2014 Nov 1;30(21):3118-9. (PMID: 25028724) BMJ Open. 2016 May 04;6(5):e011181. (PMID: 27147390) OMICS. 2012 May;16(5):284-7. (PMID: 22455463) Nat Genet. 2016 Oct;48(10):1284-1287. (PMID: 27571263) Annu Rev Pathol. 2019 Jan 24;14:421-447. (PMID: 30355152) Elife. 2018 May 30;7:. (PMID: 29846171) Bioinformatics. 2018 Aug 1;34(15):2538-2545. (PMID: 29579179) Circulation. 2013 Mar 12;127(10):1105-15. (PMID: 23393012) PLoS Negl Trop Dis. 2011;5(5):e992. (PMID: 21655351) Parasitol Int. 2022 Apr;87:102530. (PMID: 34929405) Rev Inst Med Trop Sao Paulo. 2021 Apr 23;63:e31. (PMID: 33909845) J Infect Dis. 2017 Feb 1;215(3):387-395. (PMID: 28003350) Oxid Med Cell Longev. 2021 Dec 23;2021:4993452. (PMID: 34976301) Front Cell Infect Microbiol. 2021 Nov 02;11:713150. (PMID: 34796122) Infect Immun. 2007 Apr;75(4):1886-94. (PMID: 17283096) Medicine (Baltimore). 2020 Dec 18;99(51):e23773. (PMID: 33371145) Cytokine Growth Factor Rev. 2021 Dec;62:15-22. (PMID: 34696979) Hum Immunol. 2014 Jan;75(1):20-8. (PMID: 24071371) Parasite Immunol. 2019 Oct;41(10):e12663. (PMID: 31309590) Curr Opin Neurol. 2021 Jun 1;34(3):439-446. (PMID: 33709976) Front Genet. 2021 Sep 29;12:728526. (PMID: 34659352) Glob Heart. 2015 Sep;10(3):139-44. (PMID: 26407508) PLoS Negl Trop Dis. 2021 Apr 7;15(4):e0008964. (PMID: 33826636) J Autoimmun. 2001 Aug;17(1):99-107. (PMID: 11488642) N Engl J Med. 2015 Oct;373(14):1295-306. (PMID: 26323937) Clin Infect Dis. 2021 Aug 16;73(4):672-679. (PMID: 33539531) PLoS Negl Trop Dis. 2018 Jun 4;12(6):e0006559. (PMID: 29864133) PLoS Negl Trop Dis. 2021 Feb 4;15(2):e0009059. (PMID: 33539379) Immunobiology. 2022 Jan;227(1):152166. (PMID: 34936965) Front Immunol. 2018 Aug 24;9:1929. (PMID: 30197647) |
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 |
تدمد: | 1935-2735 |
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DOI: | 10.1371/journal.pntd.0010725 |