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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lee, Kwang Seob 
Kronbichler, Andreas  ORCID logo  https://orcid.org/0000-0002-2945-2946
Pereira Vasconcelos, Daniel Fernando  ORCID logo  https://orcid.org/0000-0002-3331-452X
Pereira da Silva, Felipe Rodolfo  ORCID logo  https://orcid.org/0000-0001-9224-5571
Ko, Younhee 

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.

Description

Keywords

antineutrophil cytoplasmic antibody (ANCA), genome-wide association study, meta-analysis, myeloperoxidase, proteinase 3, single nucleotide polymorphism, vasculitis

Journal Title

J Clin Med

Conference Name

Journal ISSN

2077-0383
2077-0383

Volume Title

8

Publisher

MDPI AG