Tsai F.-J.Lee Y.-C.Chang J.-S.LI-MIN HUANGHuang F.-Y.Chiu N.-C.Chen M.-R.Chi H.Lee Y.-J.Chang L.-C.Liu Y.-M.Wang H.-H.Chen C.-H.Chen Y.-T.Wu J.-Y.2021-06-242021-06-2420111932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-79951546145&doi=10.1371%2fjournal.pone.0016853&partnerID=40&md5=95299b678f279b4f760c6d391a9705aahttps://scholars.lib.ntu.edu.tw/handle/123456789/566507Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10-5), rs4243399 (p = 9.93×10-5), and rs16849083 (p = 9.93×10-5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10-5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10-5 and 8.93×10-6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD. ? 2011 Tsai et al.[SDGs]SDG3cell protein; coatomer protein; coatomer protein complex beta 2 subunit; endoplasmic reticulum amino peptidase 1; glutamate carboxypeptidase II; HLA A antigen; HLA B antigen; immunoglobulin heavy chain; mitochondrial protein; mitochondrial ribosomal protein S22; retinol binding protein; retinol binding protein 2; tumor necrosis factor alpha; unclassified drug; article; Chinese; controlled study; gene frequency; gene linkage disequilibrium; gene locus; genetic association; genetic predisposition; genetic susceptibility; genotype; haplotype map; human; immune response; intron; major clinical study; mucocutaneous lymph node syndrome; phenotype; risk factor; single nucleotide polymorphism; Taiwan; Asian; case control study; ethnology; female; genetic association; genetic predisposition; genetics; infant; male; population genetics; preschool child; validation study; Asian Continental Ancestry Group; Case-Control Studies; Child, Preschool; Female; Genetic Loci; Genetic Predisposition to Disease; Genetics, Population; Genome-Wide Association Study; Genotype; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Polymorphism, Single Nucleotidejournal article10.1371/journal.pone.0016853213268602-s2.0-79951546145