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A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease

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Abstract

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15–25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p < 1 × 10−5). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85–4.54, P combined = 1.46 × 10−6); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77–4.12, P combined = 2.00 × 10−6). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.

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Abbreviations

CAL:

Coronary artery lesion

CI:

Confidence interval

GWAS:

Genome-wide association study

HWE:

Hardy–Weinberg equilibrium

IBS:

Identity-by-state

KD:

Kawasaki disease

KKDGC:

Korean Kawasaki Disease Genetics Consortium

LD:

Linkage disequilibrium

MAF:

Minor allele frequency

nsSNP:

Nonsynonymous SNP

OR:

Odds ratio

SNP:

Single nucleotide polymorphism

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Acknowledgments

We thank all patients with Kawasaki disease and their families for participating in this study. We also thank Dr. Kyunga Kim and Dr. Sang-Hoon Moon for statistical and bioinformatics support, respectively. This work was supported by a grant from the Ministry of Health & Welfare of the Republic of Korea (A010384).

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The authors declare no conflict of interest.

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Correspondence to In-Sook Park or Jong-Keuk Lee.

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Details of the Korean Kawasaki Disease Genetics Consortium are given in the Appendix.

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Appendix: Korean Kawasaki Disease Genetics Consortium

Appendix: Korean Kawasaki Disease Genetics Consortium

In-Sook Park, Jeong-Jin Yoo, Soo-Jong Hong, Kwi-Joo Kim (Department of Pediatrics, Asan Medical Center, Seoul, Korea); Jong-Keuk Lee, Jae-Jung Kim, Young-Mi Park (Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea); Young Mi Hong, Saejung Sohn (Department of Pediatrics, Ewha Womans University Hospital, Seoul, Korea); Gi Young Jang, Kee-Soo Ha, Hyo-Kyoung Nam, Jung-Hye Byeon (Department of Pediatrics, Korea University Hospital, Seoul, Korea); Sin Weon Yun (Department of Pediatrics, Chung-Ang University Hospital, Seoul, Korea); Myung Ki Han (Department of Pediatrics, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea); Kyung-Yil Lee, Ja-Young Hwang, Jung-Woo Rhim (Department of Pediatrics, The Catholic University of Korea, Daejeon St. Mary’s Hospital, Daejeon, Korea); Min Seob Song (Department of Pediatrics, Inje University Paik Hospital, Busan, Korea); Hyoung Doo Lee (Department of Pediatrics, Pusan National University Hospital, Busan, Korea); Dong Soo Kim (Department of Pediatrics, Yonsei University College of Medicine, Severance Children’s Hospital, Seoul, Korea); Jae-Moo Lee (Seoul Clinical Laboratories, Seoul, Korea).

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Kim, JJ., Hong, Y.M., Sohn, S. et al. A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease. Hum Genet 129, 487–495 (2011). https://doi.org/10.1007/s00439-010-0937-x

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  • DOI: https://doi.org/10.1007/s00439-010-0937-x

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