title: Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.
abstract: Kawasaki 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, p(best) = 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 p(best)-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.
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lee
authors.forename: Jeng-Sheng
authors.initials: JS
authors.lastname: Chang
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.forename: Fu-Yuan
authors.initials: FY
authors.lastname: Huang
authors.forename: Nan-Chang
authors.initials: NC
authors.lastname: Chiu
authors.forename: Ming-Ren
authors.initials: MR
authors.lastname: Chen
authors.forename: Hsin
authors.initials: H
authors.lastname: Chi
authors.forename: Yann-Jinn
authors.initials: YJ
authors.lastname: Lee
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Hsiang-Hua
authors.initials: HH
authors.lastname: Wang
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide