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Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease

Title: Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease
Authors: Hoggart, C
Shimizu, C
Galassini, R
Wright, VJ
Shailes, H
Bellos, E
Herberg, JA
Pollard, AJ
O'Connor, D
Choi, SW
Seaby, EG
Menikou, S
Hibberd, M
Sallah, N
Burgner, D
Brogan, P
Patel, H
Kim, J
Tremoulet, AH
Salo, E
Van Stijn, D
Kuijpers, T
Burns, JC
Levin, M
Item Type: Journal Article
Abstract: Kawasaki disease (KD) is a paediatric vasculitis associated with coronary artery aneurysms (CAA). Genetic variants influencing susceptibility to KD have been previously identified, but no risk alleles have been validated that influence CAA formation. We conducted a genome-wide association study (GWAS) for CAA in KD patients of European descent with 200 cases and 276 controls. A second GWAS for susceptibility pooled KD cases with healthy paediatric controls from vaccine trials in the UK (n = 1609). Logistic regression mixed models were used for both GWASs. The susceptibility GWAS was meta-analysed with 400 KD cases and 6101 controls from a previous European GWAS, these results were further meta-analysed with Japanese GWASs at two putative loci. The CAA GWAS identified an intergenic region of chromosome 20q13 with multiple SNVs showing genome-wide significance. The risk allele of the most associated SNV (rs6017006) was present in 13% of cases and 4% of controls; in East Asian 1000 Genomes data, the allele was absent or rare. Susceptibility GWAS with meta-analysis with previously published European data identified two previously associated loci (ITPKC and FCGR2A). Further meta-analysis with Japanese GWAS summary data from the CASP3 and FAM167A genomic regions validated these loci in Europeans showing consistent effects of the top SNVs in both populations. We identified a novel locus for CAA in KD patients of European descent. The results suggest that different genes determine susceptibility to KD and development of CAA and future work should focus on the function of the intergenic region on chromosome 20q13.
Issue Date: 26-Mar-2021
Date of Acceptance: 18-Feb-2021
URI: http://hdl.handle.net/10044/1/88213
DOI: 10.1038/s41431-021-00838-5
ISSN: 1018-4813
Publisher: Springer Nature [academic journals on nature.com]
Journal / Book Title: European Journal of Human Genetics
Copyright Statement: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: European Commission
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 279185
RDA02
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
International Kawasaki Disease Genetics Consortium
UK Kawasaki Disease Genetics Consortium
EUCLIDS Consortium
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
Genetics & Heredity
0604 Genetics
1103 Clinical Sciences
Publication Status: Published online
Online Publication Date: 2021-03-26
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons