A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease

Jae Jung Kim, Sin Weon Yun, Jeong Jin Yu, Kyung Lim Yoon, Kyung Yil Lee, Hong Ryang Kil, Gi Beom Kim, Myung Ki Han, Min Seob Song, Hyoung Doo Lee, Kee Soo Ha, Sejung Sohn, Todd A. Johnson, Atsushi Takahashi, Michiaki Kubo, Tatsuhiko Tsunoda, Kaoru Ito, Yoshihiro Onouchi, Young Mi Hong, Gi Young JangJong Keuk Lee

Research output: Contribution to journalArticle

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Abstract

Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (Po1.0 × 10-5), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10-11). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10-6) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10-6 to 5.24 × 10-8). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10-6). These results provide new insights into the pathogenesis and pathophysiology of KD.

Original languageEnglish
Pages (from-to)1023-1029
Number of pages7
JournalJournal of Human Genetics
Volume62
Issue number12
DOIs
Publication statusPublished - 01-12-2017

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Mucocutaneous Lymph Node Syndrome
Genome-Wide Association Study
Disease Susceptibility
HLA Antigens
Odds Ratio
Single Nucleotide Polymorphism
Chromosomes
Systemic Vasculitis
Fever
Inflammation
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Kim, J. J., Yun, S. W., Yu, J. J., Yoon, K. L., Lee, K. Y., Kil, H. R., ... Lee, J. K. (2017). A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease. Journal of Human Genetics, 62(12), 1023-1029. https://doi.org/10.1038/jhg.2017.87
Kim, Jae Jung ; Yun, Sin Weon ; Yu, Jeong Jin ; Yoon, Kyung Lim ; Lee, Kyung Yil ; Kil, Hong Ryang ; Kim, Gi Beom ; Han, Myung Ki ; Song, Min Seob ; Lee, Hyoung Doo ; Ha, Kee Soo ; Sohn, Sejung ; Johnson, Todd A. ; Takahashi, Atsushi ; Kubo, Michiaki ; Tsunoda, Tatsuhiko ; Ito, Kaoru ; Onouchi, Yoshihiro ; Hong, Young Mi ; Jang, Gi Young ; Lee, Jong Keuk. / A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease. In: Journal of Human Genetics. 2017 ; Vol. 62, No. 12. pp. 1023-1029.
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abstract = "Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (Po1.0 × 10-5), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10-11). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10-6) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10-6 to 5.24 × 10-8). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10-6). These results provide new insights into the pathogenesis and pathophysiology of KD.",
author = "Kim, {Jae Jung} and Yun, {Sin Weon} and Yu, {Jeong Jin} and Yoon, {Kyung Lim} and Lee, {Kyung Yil} and Kil, {Hong Ryang} and Kim, {Gi Beom} and Han, {Myung Ki} and Song, {Min Seob} and Lee, {Hyoung Doo} and Ha, {Kee Soo} and Sejung Sohn and Johnson, {Todd A.} and Atsushi Takahashi and Michiaki Kubo and Tatsuhiko Tsunoda and Kaoru Ito and Yoshihiro Onouchi and Hong, {Young Mi} and Jang, {Gi Young} and Lee, {Jong Keuk}",
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Kim, JJ, Yun, SW, Yu, JJ, Yoon, KL, Lee, KY, Kil, HR, Kim, GB, Han, MK, Song, MS, Lee, HD, Ha, KS, Sohn, S, Johnson, TA, Takahashi, A, Kubo, M, Tsunoda, T, Ito, K, Onouchi, Y, Hong, YM, Jang, GY & Lee, JK 2017, 'A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease', Journal of Human Genetics, vol. 62, no. 12, pp. 1023-1029. https://doi.org/10.1038/jhg.2017.87

A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease. / Kim, Jae Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung Yil; Kil, Hong Ryang; Kim, Gi Beom; Han, Myung Ki; Song, Min Seob; Lee, Hyoung Doo; Ha, Kee Soo; Sohn, Sejung; Johnson, Todd A.; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Ito, Kaoru; Onouchi, Yoshihiro; Hong, Young Mi; Jang, Gi Young; Lee, Jong Keuk.

In: Journal of Human Genetics, Vol. 62, No. 12, 01.12.2017, p. 1023-1029.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease

AU - Kim, Jae Jung

AU - Yun, Sin Weon

AU - Yu, Jeong Jin

AU - Yoon, Kyung Lim

AU - Lee, Kyung Yil

AU - Kil, Hong Ryang

AU - Kim, Gi Beom

AU - Han, Myung Ki

AU - Song, Min Seob

AU - Lee, Hyoung Doo

AU - Ha, Kee Soo

AU - Sohn, Sejung

AU - Johnson, Todd A.

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Tsunoda, Tatsuhiko

AU - Ito, Kaoru

AU - Onouchi, Yoshihiro

AU - Hong, Young Mi

AU - Jang, Gi Young

AU - Lee, Jong Keuk

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (Po1.0 × 10-5), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10-11). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10-6) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10-6 to 5.24 × 10-8). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10-6). These results provide new insights into the pathogenesis and pathophysiology of KD.

AB - Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (Po1.0 × 10-5), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10-11). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10-6) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10-6 to 5.24 × 10-8). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10-6). These results provide new insights into the pathogenesis and pathophysiology of KD.

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