title: Genome-Wide Association Study Identifies Novel Susceptibility Genes Associated with Coronary Artery Aneurysm Formation in Kawasaki Disease.
abstract: Kawasaki disease (KD) or Kawasaki syndrome is known as a vasculitis of small to medium-sized vessels, and coronary arteries are predominantly involved in childhood. Generally, 20-25% of untreated with IVIG and 3-5% of treated KD patients have been developed coronary artery lesions (CALs), such as dilatation and aneurysm. Understanding how coronary artery aneurysms (CAAs) are established and maintained in KD patients is therefore of great importance. Upon our previous genotyping data of 157 valid KD subjects, a genome-wide association study (GWAS) has been conducted among 11 (7%) CAA-developed KD patients to reveal five significant genetic variants passed pre-defined thresholds and resulted in two novel susceptibility protein-coding genes, which are NEBL (rs16921209 (P = 7.44 × 10(-9); OR = 32.22) and rs7922552 (P = 8.43 × 10(-9); OR = 32.0)) and TUBA3C (rs17076896 (P = 8.04 × 10(-9); OR = 21.03)). Their known functions have been reported to associate with cardiac muscle and tubulin, respectively. As a result, this might imply their putative roles of establishing CAAs during KD progression. Additionally, various model analyses have been utilized to determine dominant and recessive inheritance patterns of identified susceptibility mutations. Finally, all susceptibility genes hit by significant genetic variants were further investigated and the top three representative gene-ontology (GO) clusters were regulation of cell projection organization, neuron recognition, and peptidyl-threonine phosphorylation. Our results help to depict the potential routes of the pathogenesis of CAAs in KD patients and will facilitate researchers to improve the diagnosis and prognosis of KD in personalized medicine.
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sung-Chou
authors.initials: SC
authors.lastname: Li
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mindy Ming-Huey
authors.initials: MM
authors.lastname: Guo
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hong-Ren
authors.initials: HR
authors.lastname: Yu
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Huang
authors.affiliation: Children's Hospital of Shaanxi Provincial People's Hospital and Jiaotong University, Xi'an, China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Jiao
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Center for Research Informatics, The University of Chicago, Chicago, Illinois, 60637, United States of America.
authors.forename: Jorge
authors.initials: J
authors.lastname: Andrade
authors.affiliation: Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Center for Research Informatics, The University of Chicago, Chicago, Illinois, 60637, United States of America.
authors.forename: Wen-Ching
authors.identifier: 0000-0003-0034-7277
authors.initials: WC
authors.lastname: Chan
mesh_terms: D002648:Child; D003323:Coronary Aneurysm / Q000150:complications* / Q000235:genetics*; D003331:Coronary Vessels / Q000473:pathology*; D063990:Gene Ontology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008957:Models, Genetic; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9