TY - JOUR
T1 - Genetic variants in antineutrophil cytoplasmic antibody-associated vasculitis
T2 - A bayesian approach and systematic review
AU - Lee, Kwang Seob
AU - Kronbichler, Andreas
AU - Pereira Vasconcelos, Daniel Fernando
AU - Da Silva, Felipe Rodolfo Pereira
AU - Ko, Younhee
AU - Oh, Yeon Su
AU - Eisenhut, Michael
AU - Merkel, Peter A.
AU - Jayne, David
AU - Amos, Christopher I.
AU - Siminovitch, Katherine A.
AU - Rahmattulla, Chinar
AU - Lee, Keum Hwa
AU - Shin, Jae Il
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/2
Y1 - 2019/2
N2 - 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-) signaling pathway”. By using FPRP and BFDP, network analysis of noteworthy genetic variants discovered genetic risk factors associated with the IFN- pathway as novel mechanisms potentially implicated in the complex pathogenesis of ANCA-associated vasculitis.
AB - 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-) signaling pathway”. By using FPRP and BFDP, network analysis of noteworthy genetic variants discovered genetic risk factors associated with the IFN- pathway as novel mechanisms potentially implicated in the complex pathogenesis of ANCA-associated vasculitis.
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U2 - 10.3390/jcm8020266
DO - 10.3390/jcm8020266
M3 - Article
AN - SCOPUS:85075795661
SN - 2077-0383
VL - 8
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 2
M1 - 266
ER -