Proceedings of the National Academy of Sciences · 2018 · 89 citations · 36 references
Life SciencesGeneticsImmunologyAutoimmunityGenomicsImmunogeneticsAortic DiseaseAutoimmune DiseasesDisease Susceptibility LociGenetic RiskGenetic Susceptibility To AutoimmunityGenome-wide Association StudiesEpistasis AnalysisGenetic Susceptibility To VasculitisNon-human Leukocyte Antigen Risk LociSingle-variant Association AnalysisSystemic VasculitisTakayasu ArteritisVascular InvolvementVasculitis Pathogenesis
Significance Takayasu arteritis (TAK) is a systemic vasculitis with unknown etiology. We identified four unreported susceptibility genes to TAK through genome-wide association studies. We successfully fine-mapped HLA associations and showed that HLA-G is associated with TAK in addition to HLA-B*52. The association between PTK2B and TAK could be explained by expression regulation of PTK2B. We showed an epistasis effect of LILR3A, one of the four genes, with HLA-B52 on TAK susceptibility. Enhancer enrichment analysis of significant non-HLA markers showed natural killer cells as important cells in TAK. Not only the associations in the HLA region but also nonsignificant associations from GWAS suggest the involvement of NK cells. These findings would lead to a better understanding of TAK.
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Haploview: analysis and visualization of LD and haplotype maps
Jeffrey C. Barrett, Ben Fry, Julian Maller et al. · Bioinformatics · 2004 · 14.7K citations · Full text
The Genotype-Tissue Expression (GTEx) project.
A map of human genome variation from population-scale sequencing