Genome-wide association study identifies novel Colony Stimulating Factor 1 locus conferring susceptibility to cryptococcosis in HIV-infected South Africans. Kannambath, S., Jarvis, J. N, Wake, R. M, Longley, N., Loyse, A., Matzaraki, V., Aguirre-Gamboa, R., Wijmenga, C., Doyle, R., Paximadis, M., Tiemessen, C. T, Kumar, V., Pittman, A., Meintjes, G. A, Harrison, T. S, Netea, M. G, & Bicanic, T. Open Forum Infectious Diseases, 7(11):ofaa489, oct, 2020. ![Genome-wide association study identifies novel Colony Stimulating Factor 1 locus conferring susceptibility to cryptococcosis in HIV-infected South Africans [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background: Cryptococcus is the most common cause of meningitis in human immunodeficiency virus (HIV)-infected Africans. Despite universal exposure, only 5%-10% of patients with HIV/acquired immune deficiency syndrome and profound CD4+ T-cell depletion develop disseminated cryptococcosis: host genetic factors may play a role. Prior targeted immunogenetic studies in cryptococcosis have comprised few Africans. Methods: We analyzed genome-wide single-nucleotide polymorphism (SNP) genotype data from 524 patients of African descent: 243 cases (advanced HIV with cryptococcal antigenemia and/or cryptococcal meningitis) and 281 controls (advanced HIV, no history of cryptococcosis, negative serum cryptococcal antigen). Results: Six loci upstream of the colony-stimulating factor 1 (CSF1) gene, encoding macrophage colony-stimulating factor (M-CSF) were associated with susceptibility to cryptococcosis at P\textless10-6 and remained significantly associated in a second South African cohort (83 cases; 128 controls). Meta-analysis of the genotyped CSF1 SNP rs1999713 showed an odds ratio for cryptococcosis susceptibility of 0.53 (95% confidence interval, 0.42-0.66; P=5.96×10-8). Ex vivo functional validation and transcriptomic studies confirmed the importance of macrophage activation by M-CSF in host defence against Cryptococcus in HIV-infected patients and healthy, ethnically matched controls. Conclusions: This first genome-wide association study of susceptibility to cryptococcosis has identified novel and immunologically relevant susceptibility loci, which may help define novel strategies for prevention or immunotherapy of HIV-associated cryptococcal meningitis.
@article{Kannambath2020,
abstract = {Background: Cryptococcus is the most common cause of meningitis in human immunodeficiency virus (HIV)-infected Africans. Despite universal exposure, only 5{\%}-10{\%} of patients with HIV/acquired immune deficiency syndrome and profound CD4+ T-cell depletion develop disseminated cryptococcosis: host genetic factors may play a role. Prior targeted immunogenetic studies in cryptococcosis have comprised few Africans. Methods: We analyzed genome-wide single-nucleotide polymorphism (SNP) genotype data from 524 patients of African descent: 243 cases (advanced HIV with cryptococcal antigenemia and/or cryptococcal meningitis) and 281 controls (advanced HIV, no history of cryptococcosis, negative serum cryptococcal antigen). Results: Six loci upstream of the colony-stimulating factor 1 (CSF1) gene, encoding macrophage colony-stimulating factor (M-CSF) were associated with susceptibility to cryptococcosis at P{\textless}10-6 and remained significantly associated in a second South African cohort (83 cases; 128 controls). Meta-analysis of the genotyped CSF1 SNP rs1999713 showed an odds ratio for cryptococcosis susceptibility of 0.53 (95{\%} confidence interval, 0.42-0.66; P=5.96×10-8). Ex vivo functional validation and transcriptomic studies confirmed the importance of macrophage activation by M-CSF in host defence against Cryptococcus in HIV-infected patients and healthy, ethnically matched controls. Conclusions: This first genome-wide association study of susceptibility to cryptococcosis has identified novel and immunologically relevant susceptibility loci, which may help define novel strategies for prevention or immunotherapy of HIV-associated cryptococcal meningitis.},
author = {Kannambath, Shichina and Jarvis, Joseph N and Wake, Rachel M and Longley, Nicky and Loyse, Angela and Matzaraki, Vicky and Aguirre-Gamboa, Ra{\'{u}}l and Wijmenga, Cisca and Doyle, Ronan and Paximadis, Maria and Tiemessen, Caroline T and Kumar, Vinod and Pittman, Alan and Meintjes, Graeme A and Harrison, Thomas S and Netea, Mihai G and Bicanic, Tihana},
doi = {10.1093/ofid/ofaa489},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kannambath et al. - 2020 - Genome-wide association study identifies novel Colony Stimulating Factor 1 locus conferring susceptibility to.pdf:pdf;:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kannambath et al. - 2020 - Genome-wide association study identifies novel Colony Stimulating Factor 1 locus conferring susceptibility(2).pdf:pdf},
issn = {2328-8957},
journal = {Open Forum Infectious Diseases},
keywords = {OA,cryptococcal meningitis,cryptococcosis,cryptococcus,fund{\_}ack,genome-wide association study,hiv,hiv infections,macrophage colony-stimulating factor,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {oct},
number = {11},
pages = {ofaa489},
pmid = {33269293},
title = {{Genome-wide association study identifies novel Colony Stimulating Factor 1 locus conferring susceptibility to cryptococcosis in HIV-infected South Africans}},
url = {https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa489/5925041},
volume = {7},
year = {2020}
}
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Prior targeted immunogenetic studies in cryptococcosis have comprised few Africans. Methods: We analyzed genome-wide single-nucleotide polymorphism (SNP) genotype data from 524 patients of African descent: 243 cases (advanced HIV with cryptococcal antigenemia and/or cryptococcal meningitis) and 281 controls (advanced HIV, no history of cryptococcosis, negative serum cryptococcal antigen). Results: Six loci upstream of the colony-stimulating factor 1 (CSF1) gene, encoding macrophage colony-stimulating factor (M-CSF) were associated with susceptibility to cryptococcosis at P\\textless10-6 and remained significantly associated in a second South African cohort (83 cases; 128 controls). Meta-analysis of the genotyped CSF1 SNP rs1999713 showed an odds ratio for cryptococcosis susceptibility of 0.53 (95% confidence interval, 0.42-0.66; P=5.96×10-8). Ex vivo functional validation and transcriptomic studies confirmed the importance of macrophage activation by M-CSF in host defence against Cryptococcus in HIV-infected patients and healthy, ethnically matched controls. 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