A genome-wide association study identifies three new risk loci for Kawasaki disease

Yoshihiro Onouchi; Kouichi Ozaki; Jane C. Burns; Chisato Shimizu; Masaru Terai; Hiromichi Hamada; Takafumi Honda; Hiroyuki Suzuki; Tomohiro Suenaga; Takashi Takeuchi; Norishige Yoshikawa; Yoichi Suzuki; Kumi Yasukawa; Ryota Ebata; Kouji Higashi; Tsutomu Saji; Yasushi Kemmotsu; Shinichi Takatsuki; Kazunobu Ouchi; Fumio Kishi; Tetsushi Yoshikawa; Toshiro Nagai; Kunihiro Hamamoto; Yoshitake Sato; Akihito Honda; Hironobu Kobayashi; Junichi Sato; Shoichi Shibuta; Masakazu Miyawaki; Ko Oishi; Hironobu Yamaga; Noriyuki Aoyagi; Seiji Iwahashi; Ritsuko Miyashita; Yuji Murata; Kumiko Sasago; Atsushi Takahashi; Naoyuki Kamatani; Michiaki Kubo; Tatsuhiko Tsunoda; Akira Hata; Yusuke Nakamura; Toshihiro Tanaka; Jun Abe; Tohru Kobayashi; Hirokazu Arakawa; Fukiko Ichida; Yuichi Nomura; Masaru Miura; Kazuyuki Ikeda; Toshiro Hara; Ryuji Fukazawa; Shunichi Ogawa; Kenji Hamaoka; Jane W. Newburger; Annette L. Baker; Anne H. Rowley; Stanford T. Shulman; Marian E. Melish; Wilbert H. Mason; Masato Takahashi; Adriana H. Tremoulet

doi:10.1038/ng.2220

A genome-wide association study identifies three new risk loci for Kawasaki disease

Yoshihiro Onouchi^*, Kouichi Ozaki, Jane C. Burns, Chisato Shimizu, Masaru Terai, Hiromichi Hamada, Takafumi Honda, Hiroyuki Suzuki, Tomohiro Suenaga, Takashi Takeuchi, Norishige Yoshikawa, Yoichi Suzuki, Kumi Yasukawa, Ryota Ebata, Kouji Higashi, Tsutomu Saji, Yasushi Kemmotsu, Shinichi Takatsuki, Kazunobu Ouchi, Fumio KishiTetsushi Yoshikawa, Toshiro Nagai, Kunihiro Hamamoto, Yoshitake Sato, Akihito Honda, Hironobu Kobayashi, Junichi Sato, Shoichi Shibuta, Masakazu Miyawaki, Ko Oishi, Hironobu Yamaga, Noriyuki Aoyagi, Seiji Iwahashi, Ritsuko Miyashita, Yuji Murata, Kumiko Sasago, Atsushi Takahashi, Naoyuki Kamatani, Michiaki Kubo, Tatsuhiko Tsunoda, Akira Hata, Yusuke Nakamura, Toshihiro Tanaka, Jun Abe, Tohru Kobayashi, Hirokazu Arakawa, Fukiko Ichida, Yuichi Nomura, Masaru Miura, Kazuyuki Ikeda, Toshiro Hara, Ryuji Fukazawa, Shunichi Ogawa, Kenji Hamaoka, Jane W. Newburger, Annette L. Baker, Anne H. Rowley, Stanford T. Shulman, Marian E. Melish, Wilbert H. Mason, Masato Takahashi, Adriana H. Tremoulet

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

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Abstract

We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10 ^-21), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10 ^-11) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10 ^-8). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10 ^-6) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.

Original language	English (US)
Pages (from-to)	517-521
Number of pages	5
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2220
State	Published - May 2012

Funding

We thank the individuals with Kawasaki disease and their families as well as all the medical staff taking care of them. We also thank members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan and members of the BioBank Japan project for supporting the study. We are grateful to T. Matsubara, M. Noshibatake, H. Aotsuka, H. Nakajima, F. Kudo, T. Sano, T. Matsushita, K. Suzuki, K. Akagi, T. Isobe, S. Ogita, S. Oku, T. Tanaka, Y. Tanaka, Y. Nomura, M. Sakauchi, H. Cho, A. Nariai, M. Miura, M. Nakagawa, Y. Kaburagi and other pediatricians who contributed Japanese DNA samples. We are also grateful to J. Pancheri and N. Innocentini for collecting US DNA samples. We thank D.A. Scherrer, S. Kawakami and Y. Nakashima for technical assistance. This work was supported by grants from the Millennium Project, from the Japan Kawasaki Disease Research Center and from the Ministry of Health, Labour and Welfare (0401040 to A.H.) and by a grant from the Heart, Lung, and Blood Institute of the US National Institutes of Health (HL-06941 to J.C.B.).

ASJC Scopus subject areas

Genetics

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10.1038/ng.2220

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Onouchi, Y., Ozaki, K., Burns, J. C., Shimizu, C., Terai, M., Hamada, H., Honda, T., Suzuki, H., Suenaga, T., Takeuchi, T., Yoshikawa, N., Suzuki, Y., Yasukawa, K., Ebata, R., Higashi, K., Saji, T., Kemmotsu, Y., Takatsuki, S., Ouchi, K., ... Tremoulet, A. H. (2012). A genome-wide association study identifies three new risk loci for Kawasaki disease. Nature Genetics, 44(5), 517-521. https://doi.org/10.1038/ng.2220

@article{32cf67b925b340cd9974f50a7ea541a8,

title = "A genome-wide association study identifies three new risk loci for Kawasaki disease",

abstract = "We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10 -21), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10 -11) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10 -8). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10 -6) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.",

author = "Yoshihiro Onouchi and Kouichi Ozaki and Burns, {Jane C.} and Chisato Shimizu and Masaru Terai and Hiromichi Hamada and Takafumi Honda and Hiroyuki Suzuki and Tomohiro Suenaga and Takashi Takeuchi and Norishige Yoshikawa and Yoichi Suzuki and Kumi Yasukawa and Ryota Ebata and Kouji Higashi and Tsutomu Saji and Yasushi Kemmotsu and Shinichi Takatsuki and Kazunobu Ouchi and Fumio Kishi and Tetsushi Yoshikawa and Toshiro Nagai and Kunihiro Hamamoto and Yoshitake Sato and Akihito Honda and Hironobu Kobayashi and Junichi Sato and Shoichi Shibuta and Masakazu Miyawaki and Ko Oishi and Hironobu Yamaga and Noriyuki Aoyagi and Seiji Iwahashi and Ritsuko Miyashita and Yuji Murata and Kumiko Sasago and Atsushi Takahashi and Naoyuki Kamatani and Michiaki Kubo and Tatsuhiko Tsunoda and Akira Hata and Yusuke Nakamura and Toshihiro Tanaka and Jun Abe and Tohru Kobayashi and Hirokazu Arakawa and Fukiko Ichida and Yuichi Nomura and Masaru Miura and Kazuyuki Ikeda and Toshiro Hara and Ryuji Fukazawa and Shunichi Ogawa and Kenji Hamaoka and Newburger, {Jane W.} and Baker, {Annette L.} and Rowley, {Anne H.} and Shulman, {Stanford T.} and Melish, {Marian E.} and Mason, {Wilbert H.} and Masato Takahashi and Tremoulet, {Adriana H.}",

note = "Funding Information: We thank the individuals with Kawasaki disease and their families as well as all the medical staff taking care of them. We also thank members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan and members of the BioBank Japan project for supporting the study. We are grateful to T. Matsubara, M. Noshibatake, H. Aotsuka, H. Nakajima, F. Kudo, T. Sano, T. Matsushita, K. Suzuki, K. Akagi, T. Isobe, S. Ogita, S. Oku, T. Tanaka, Y. Tanaka, Y. Nomura, M. Sakauchi, H. Cho, A. Nariai, M. Miura, M. Nakagawa, Y. Kaburagi and other pediatricians who contributed Japanese DNA samples. We are also grateful to J. Pancheri and N. Innocentini for collecting US DNA samples. We thank D.A. Scherrer, S. Kawakami and Y. Nakashima for technical assistance. This work was supported by grants from the Millennium Project, from the Japan Kawasaki Disease Research Center and from the Ministry of Health, Labour and Welfare (0401040 to A.H.) and by a grant from the Heart, Lung, and Blood Institute of the US National Institutes of Health (HL-06941 to J.C.B.).",

year = "2012",

month = may,

doi = "10.1038/ng.2220",

language = "English (US)",

volume = "44",

pages = "517--521",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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Onouchi, Y, Ozaki, K, Burns, JC, Shimizu, C, Terai, M, Hamada, H, Honda, T, Suzuki, H, Suenaga, T, Takeuchi, T, Yoshikawa, N, Suzuki, Y, Yasukawa, K, Ebata, R, Higashi, K, Saji, T, Kemmotsu, Y, Takatsuki, S, Ouchi, K, Kishi, F, Yoshikawa, T, Nagai, T, Hamamoto, K, Sato, Y, Honda, A, Kobayashi, H, Sato, J, Shibuta, S, Miyawaki, M, Oishi, K, Yamaga, H, Aoyagi, N, Iwahashi, S, Miyashita, R, Murata, Y, Sasago, K, Takahashi, A, Kamatani, N, Kubo, M, Tsunoda, T, Hata, A, Nakamura, Y, Tanaka, T, Abe, J, Kobayashi, T, Arakawa, H, Ichida, F, Nomura, Y, Miura, M, Ikeda, K, Hara, T, Fukazawa, R, Ogawa, S, Hamaoka, K, Newburger, JW, Baker, AL, Rowley, AH , Shulman, ST, Melish, ME, Mason, WH, Takahashi, M & Tremoulet, AH 2012, 'A genome-wide association study identifies three new risk loci for Kawasaki disease', Nature Genetics, vol. 44, no. 5, pp. 517-521. https://doi.org/10.1038/ng.2220

TY - JOUR

T1 - A genome-wide association study identifies three new risk loci for Kawasaki disease

AU - Onouchi, Yoshihiro

AU - Ozaki, Kouichi

AU - Burns, Jane C.

AU - Shimizu, Chisato

AU - Terai, Masaru

AU - Hamada, Hiromichi

AU - Honda, Takafumi

AU - Suzuki, Hiroyuki

AU - Suenaga, Tomohiro

AU - Takeuchi, Takashi

AU - Yoshikawa, Norishige

AU - Suzuki, Yoichi

AU - Yasukawa, Kumi

AU - Ebata, Ryota

AU - Higashi, Kouji

AU - Saji, Tsutomu

AU - Kemmotsu, Yasushi

AU - Takatsuki, Shinichi

AU - Ouchi, Kazunobu

AU - Kishi, Fumio

AU - Yoshikawa, Tetsushi

AU - Nagai, Toshiro

AU - Hamamoto, Kunihiro

AU - Sato, Yoshitake

AU - Honda, Akihito

AU - Kobayashi, Hironobu

AU - Sato, Junichi

AU - Shibuta, Shoichi

AU - Miyawaki, Masakazu

AU - Oishi, Ko

AU - Yamaga, Hironobu

AU - Aoyagi, Noriyuki

AU - Iwahashi, Seiji

AU - Miyashita, Ritsuko

AU - Murata, Yuji

AU - Sasago, Kumiko

AU - Takahashi, Atsushi

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

AU - Tsunoda, Tatsuhiko

AU - Hata, Akira

AU - Nakamura, Yusuke

AU - Tanaka, Toshihiro

AU - Abe, Jun

AU - Kobayashi, Tohru

AU - Arakawa, Hirokazu

AU - Ichida, Fukiko

AU - Nomura, Yuichi

AU - Miura, Masaru

AU - Ikeda, Kazuyuki

AU - Hara, Toshiro

AU - Fukazawa, Ryuji

AU - Ogawa, Shunichi

AU - Hamaoka, Kenji

AU - Newburger, Jane W.

AU - Baker, Annette L.

AU - Rowley, Anne H.

AU - Shulman, Stanford T.

AU - Melish, Marian E.

AU - Mason, Wilbert H.

AU - Takahashi, Masato

AU - Tremoulet, Adriana H.

N1 - Funding Information: We thank the individuals with Kawasaki disease and their families as well as all the medical staff taking care of them. We also thank members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan and members of the BioBank Japan project for supporting the study. We are grateful to T. Matsubara, M. Noshibatake, H. Aotsuka, H. Nakajima, F. Kudo, T. Sano, T. Matsushita, K. Suzuki, K. Akagi, T. Isobe, S. Ogita, S. Oku, T. Tanaka, Y. Tanaka, Y. Nomura, M. Sakauchi, H. Cho, A. Nariai, M. Miura, M. Nakagawa, Y. Kaburagi and other pediatricians who contributed Japanese DNA samples. We are also grateful to J. Pancheri and N. Innocentini for collecting US DNA samples. We thank D.A. Scherrer, S. Kawakami and Y. Nakashima for technical assistance. This work was supported by grants from the Millennium Project, from the Japan Kawasaki Disease Research Center and from the Ministry of Health, Labour and Welfare (0401040 to A.H.) and by a grant from the Heart, Lung, and Blood Institute of the US National Institutes of Health (HL-06941 to J.C.B.).

PY - 2012/5

Y1 - 2012/5

N2 - We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10 -21), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10 -11) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10 -8). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10 -6) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.

AB - We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10 -21), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10 -11) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10 -8). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10 -6) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.

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U2 - 10.1038/ng.2220

DO - 10.1038/ng.2220

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AN - SCOPUS:84862794716

SN - 1061-4036

VL - 44

SP - 517

EP - 521

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

A genome-wide association study identifies three new risk loci for Kawasaki disease

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