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Genetic Variants in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Bayesian Approach and Systematic Review

Authors
 Kwang Seob Lee  ;  Andreas Kronbichler  ;  Daniel Fernando Pereira Vasconcelos  ;  Felipe Rodolfo Pereira da Silva  ;  Younhee Ko  ;  Yeon Su Oh  ;  Michael Eisenhut  ;  Peter A. Merkel  ;  David Jayne  ;  Christopher I. Amos  ;  Katherine A. Siminovitch  ;  Chinar Rahmattulla  ;  Keum Hwa Lee  ;  Jae Il Shin 
Citation
 Journal of Clinical Medicine, Vol.8(2) : E266, 2019 
Journal Title
 Journal of Clinical Medicine 
Issue Date
2019
Keywords
antineutrophil cytoplasmic antibody (ANCA) ; genome-wide association study ; meta-analysis ; myeloperoxidase ; proteinase 3 ; single nucleotide polymorphism ; vasculitis
Abstract
A number of genome-wide association studies (GWASs) and meta-analyses of genetic variants have been performed in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We reinterpreted previous studies using false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP). This study searched publications in PubMed and Excerpta Medica Database (EMBASE) up to February 2018. Identification of noteworthy associations were analyzed using FPRP and BFDP, and data (i.e., odds ratio (OR), 95% confidence interval (CI), p-value) related to significant associations were separately extracted. Using filtered gene variants, gene ontology (GO) enrichment analysis and protein⁻protein interaction (PPI) networks were performed. Overall, 241 articles were identified, and 7 were selected for analysis. Single nucleotide polymorphisms (SNPs) discovered by GWASs were shown to be noteworthy, whereas only 27% of significant results from meta-analyses of observational studies were noteworthy. Eighty-five percent of SNPs with borderline p-values (5.0 × 10-8 < p < 0.05) in GWASs were found to be noteworthy. No overlapping SNPs were found between PR3-ANCA and MPO-ANCA vasculitis. GO analysis revealed immune-related GO terms, including "antigen processing and presentation of peptide or polysaccharide antigen via major histocompatibility complex (MHC) class II", "interferon-gamma-mediated (IFN-γ) signaling pathway". By using FPRP and BFDP, network analysis of noteworthy genetic variants discovered genetic risk factors associated with the IFN-γ pathway as novel mechanisms potentially implicated in the complex pathogenesis of ANCA-associated vasculitis.
Files in This Item:
T201902406.pdf Download
DOI
10.3390/jcm8020266
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
Lee, Keum Hwa(이금화) ORCID logo https://orcid.org/0000-0002-1511-9587
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170908
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