Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population

Yukinori Okada; Chikashi Terao; Katsunori Ikari; Yuta Kochi; Koichiro Ohmura; Akari Suzuki; Takahisa Kawaguchi; Eli A. Stahl; Fina A.S. Kurreeman; Nao Nishida; Hiroko Ohmiya; Keiko Myouzen; Meiko Takahashi; Tetsuji Sawada; Yuichi Nishioka; Masao Yukioka; Tsukasa Matsubara; Shigeyuki Wakitani; Ryota Teshima; Shigeto Tohma; Kiyoshi Takasugi; Kota Shimada; Akira Murasawa; Shigeru Honjo; Keitaro Matsuo; Hideo Tanaka; Kazuo Tajima; Taku Suzuki; Takuji Iwamoto; Yoshiya Kawamura; Hisashi Tanii; Yuji Okazaki; Tsukasa Sasaki; Peter K. Gregersen; Leonid Padyukov; Jane Worthington; Katherine A. Siminovitch; Mark Lathrop; Atsuo Taniguchi; Atsushi Takahashi; Katsushi Tokunaga; Michiaki Kubo; Yusuke Nakamura; Naoyuki Kamatani; Tsuneyo Mimori; Robert M. Plenge; Hisashi Yamanaka; Shigeki Momohara; Ryo Yamada; Fumihiko Matsuda; Kazuhiko Yamamoto

doi:10.1038/ng.2231

Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population

Yukinori Okada, Chikashi Terao, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Akari Suzuki, Takahisa Kawaguchi, Eli A. Stahl, Fina A.S. Kurreeman, Nao Nishida, Hiroko Ohmiya, Keiko Myouzen, Meiko Takahashi, Tetsuji Sawada, Yuichi Nishioka, Masao Yukioka, Tsukasa Matsubara, Shigeyuki Wakitani, Ryota Teshima, Shigeto TohmaKiyoshi Takasugi, Kota Shimada, Akira Murasawa, Shigeru Honjo, Keitaro Matsuo, Hideo Tanaka, Kazuo Tajima, Taku Suzuki, Takuji Iwamoto, Yoshiya Kawamura, Hisashi Tanii, Yuji Okazaki, Tsukasa Sasaki, Peter K. Gregersen, Leonid Padyukov, Jane Worthington, Katherine A. Siminovitch, Mark Lathrop, Atsuo Taniguchi, Atsushi Takahashi, Katsushi Tokunaga, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani, Tsuneyo Mimori, Robert M. Plenge, Hisashi Yamanaka, Shigeki Momohara, Ryo Yamada, Fumihiko Matsuda, Kazuhiko Yamamoto

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Abstract

Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10 ^-8, including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves′ disease (P = 3.5 × 10 ^-4 and 2.9 × 10 ^-4, respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.

Original language	English
Pages (from-to)	511-516
Number of pages	6
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2231
State	Published - May 2012
Externally published	Yes

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Okada, Y., Terao, C., Ikari, K., Kochi, Y., Ohmura, K., Suzuki, A., Kawaguchi, T., Stahl, E. A., Kurreeman, F. A. S., Nishida, N., Ohmiya, H., Myouzen, K., Takahashi, M., Sawada, T., Nishioka, Y., Yukioka, M., Matsubara, T., Wakitani, S., Teshima, R., ... Yamamoto, K. (2012). Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nature Genetics, 44(5), 511-516. https://doi.org/10.1038/ng.2231

@article{25b8a10040714784bec5ace0977300e1,

title = "Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population",

abstract = "Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10 -8, including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves′ disease (P = 3.5 × 10 -4 and 2.9 × 10 -4, respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.",

author = "Yukinori Okada and Chikashi Terao and Katsunori Ikari and Yuta Kochi and Koichiro Ohmura and Akari Suzuki and Takahisa Kawaguchi and Stahl, {Eli A.} and Kurreeman, {Fina A.S.} and Nao Nishida and Hiroko Ohmiya and Keiko Myouzen and Meiko Takahashi and Tetsuji Sawada and Yuichi Nishioka and Masao Yukioka and Tsukasa Matsubara and Shigeyuki Wakitani and Ryota Teshima and Shigeto Tohma and Kiyoshi Takasugi and Kota Shimada and Akira Murasawa and Shigeru Honjo and Keitaro Matsuo and Hideo Tanaka and Kazuo Tajima and Taku Suzuki and Takuji Iwamoto and Yoshiya Kawamura and Hisashi Tanii and Yuji Okazaki and Tsukasa Sasaki and Gregersen, {Peter K.} and Leonid Padyukov and Jane Worthington and Siminovitch, {Katherine A.} and Mark Lathrop and Atsuo Taniguchi and Atsushi Takahashi and Katsushi Tokunaga and Michiaki Kubo and Yusuke Nakamura and Naoyuki Kamatani and Tsuneyo Mimori and Plenge, {Robert M.} and Hisashi Yamanaka and Shigeki Momohara and Ryo Yamada and Fumihiko Matsuda and Kazuhiko Yamamoto",

note = "Funding Information: The authors acknowledge the essential role of the GARNET consortium in developing the study. In this study, the following GARNET members are included: CGM of RIKEN, University of Tokyo, the BioBank Japan Project, Kyoto University and IORRA. We would like to thank all the doctors and staff who participated in sample collection for the RIKEN cohort and the BioBank Japan Project. We thank K. Kobayashi and M. Kitazato for their technical assistance. We thank T. Raj for calculation of composite of multiple signals (CMS). We thank M. Kokubo for DNA extraction, GWAS genotyping and secretarial assistance. We would also like to thank H. Yoshifuji, N. Yukawa, D. Kawabata, T. Nojima, T. Usui and T. Fujii for collecting DNA samples. We thank Y. Katagiri for her technical efforts. We also appreciate the contribution of E. Inoue and other members of the Institute of Rheumatology, Tokyo Women{\textquoteright}s Medical University, for their efforts on the IORRA cohort. This study was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, the Ministry of Health, Labour and Welfare (MHLW) in Japan, the Japan Society for the Promotion of Science (JSPS), Core Research for Evolutional Science and Technology (CREST), Solution-Oriented Research for Science and Technology (SORST), INSERM and the Okawa Foundation for Information and Telecommunications.",

year = "2012",

month = may,

doi = "10.1038/ng.2231",

language = "English",

volume = "44",

pages = "511--516",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

Okada, Y, Terao, C, Ikari, K, Kochi, Y, Ohmura, K, Suzuki, A, Kawaguchi, T, Stahl, EA, Kurreeman, FAS, Nishida, N, Ohmiya, H, Myouzen, K, Takahashi, M, Sawada, T, Nishioka, Y, Yukioka, M, Matsubara, T, Wakitani, S, Teshima, R, Tohma, S, Takasugi, K, Shimada, K, Murasawa, A, Honjo, S, Matsuo, K, Tanaka, H, Tajima, K, Suzuki, T, Iwamoto, T, Kawamura, Y, Tanii, H, Okazaki, Y, Sasaki, T, Gregersen, PK, Padyukov, L, Worthington, J, Siminovitch, KA, Lathrop, M, Taniguchi, A, Takahashi, A, Tokunaga, K, Kubo, M, Nakamura, Y, Kamatani, N, Mimori, T, Plenge, RM, Yamanaka, H, Momohara, S, Yamada, R, Matsuda, F & Yamamoto, K 2012, 'Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population', Nature Genetics, vol. 44, no. 5, pp. 511-516. https://doi.org/10.1038/ng.2231

TY - JOUR

T1 - Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population

AU - Okada, Yukinori

AU - Terao, Chikashi

AU - Ikari, Katsunori

AU - Kochi, Yuta

AU - Ohmura, Koichiro

AU - Suzuki, Akari

AU - Kawaguchi, Takahisa

AU - Stahl, Eli A.

AU - Kurreeman, Fina A.S.

AU - Nishida, Nao

AU - Ohmiya, Hiroko

AU - Myouzen, Keiko

AU - Takahashi, Meiko

AU - Sawada, Tetsuji

AU - Nishioka, Yuichi

AU - Yukioka, Masao

AU - Matsubara, Tsukasa

AU - Wakitani, Shigeyuki

AU - Teshima, Ryota

AU - Tohma, Shigeto

AU - Takasugi, Kiyoshi

AU - Shimada, Kota

AU - Murasawa, Akira

AU - Honjo, Shigeru

AU - Matsuo, Keitaro

AU - Tanaka, Hideo

AU - Tajima, Kazuo

AU - Suzuki, Taku

AU - Iwamoto, Takuji

AU - Kawamura, Yoshiya

AU - Tanii, Hisashi

AU - Okazaki, Yuji

AU - Sasaki, Tsukasa

AU - Gregersen, Peter K.

AU - Padyukov, Leonid

AU - Worthington, Jane

AU - Siminovitch, Katherine A.

AU - Lathrop, Mark

AU - Taniguchi, Atsuo

AU - Takahashi, Atsushi

AU - Tokunaga, Katsushi

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

AU - Mimori, Tsuneyo

AU - Plenge, Robert M.

AU - Yamanaka, Hisashi

AU - Momohara, Shigeki

AU - Yamada, Ryo

AU - Matsuda, Fumihiko

AU - Yamamoto, Kazuhiko

N1 - Funding Information: The authors acknowledge the essential role of the GARNET consortium in developing the study. In this study, the following GARNET members are included: CGM of RIKEN, University of Tokyo, the BioBank Japan Project, Kyoto University and IORRA. We would like to thank all the doctors and staff who participated in sample collection for the RIKEN cohort and the BioBank Japan Project. We thank K. Kobayashi and M. Kitazato for their technical assistance. We thank T. Raj for calculation of composite of multiple signals (CMS). We thank M. Kokubo for DNA extraction, GWAS genotyping and secretarial assistance. We would also like to thank H. Yoshifuji, N. Yukawa, D. Kawabata, T. Nojima, T. Usui and T. Fujii for collecting DNA samples. We thank Y. Katagiri for her technical efforts. We also appreciate the contribution of E. Inoue and other members of the Institute of Rheumatology, Tokyo Women’s Medical University, for their efforts on the IORRA cohort. This study was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, the Ministry of Health, Labour and Welfare (MHLW) in Japan, the Japan Society for the Promotion of Science (JSPS), Core Research for Evolutional Science and Technology (CREST), Solution-Oriented Research for Science and Technology (SORST), INSERM and the Okawa Foundation for Information and Telecommunications.

PY - 2012/5

Y1 - 2012/5

N2 - Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10 -8, including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves′ disease (P = 3.5 × 10 -4 and 2.9 × 10 -4, respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.

AB - Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10 -8, including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves′ disease (P = 3.5 × 10 -4 and 2.9 × 10 -4, respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.

UR - http://www.scopus.com/inward/record.url?scp=84862809846&partnerID=8YFLogxK

U2 - 10.1038/ng.2231

DO - 10.1038/ng.2231

M3 - Article

C2 - 22446963

AN - SCOPUS:84862809846

SN - 1061-4036

VL - 44

SP - 511

EP - 516

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population

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