Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head

Yuma Sakamoto; Takuaki Yamamoto; Nobuhiko Sugano; Daisuke Takahashi; Toshiyuki Watanabe; Takashi Atsumi; Junichi Nakamura; Yukiharu Hasegawa; Koichi Akashi; Ichiei Narita; Takeshi Miyamoto; Tsutomu Takeuchi; Katsunori Ikari; Koichi Amano; Atsuhiro Fujie; Toshikazu Kubo; Yoshifumi Tada; Ayumi Kaneuji; Hiroaki Nakamura; Tomoya Miyamura; Tamon Kabata; Ken Yamaji; Takahiro Okawa; Akihiro Sudo; Kenji Ohzono; Yoshiya Tanaka; Yuji Yasunaga; Shuichi Matsuda; Yuuki Imai; Yasuharu Nakashima; Goro Motomura; Satoshi Ikemura; Ryosuke Yamaguchi; Kazuyuki Karasuyama; Kazuhiko Sonoda; Takashi Nishii; Takashi Sakai; Masaki Takao; Tohru Irie; Tsuyoshi Asano; Norimasa Iwasaki; Tatsuya Atsumi; Satoshi Tamaoki; Ryosuke Nakanishi; Satoe Tanabe; Shunji Kishida; Shigeo Hagiwara; Taisuke Seki; Hiroshi Tsukamoto; Hiroaki Niiro; Yojiro Arinobu; Mitsuteru Akahoshi; Hiroshi Mitoma; Masahiro Ayano; Takeshi Kuroda; Yoshiaki Toyama; Atsushi Funayama; Hironari Hanaoka; Kunihiro Yamaoka; Yasushi Kawaguchi; Hisashi Yamanaka; Tetsuji Hosozawa; Shigeki Momohara; Kentaro Chino; Mikihiro Fujioka; Keichiro Ueshima; Masashi Ishida; Masazumi Saito; Shigeki Hayashi; Akira Ikegami; Toru Ichiseki; Shigekazu Mizokawa; Yoichi Ohta; Yoshitomo Kajino; Fumio Sekiya; Fujio Higuchi; Masahiro Hasegawa; Noriki Miyamoto; Shinichi Miyazaki; Toshio Yamaguchi; Wataru Ando; Kazuyoshi Saito; Kazuhisa Nakano; Yutaka Kuroda; Takuma Yamasaki; Masato Akiyama; Michiaki Kubo; Yoichiro Kamatani; Yukihide Iwamoto; Shiro Ikegawa

doi:10.1038/s41598-017-14778-y

Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head

Yuma Sakamoto, Takuaki Yamamoto, Nobuhiko Sugano, Daisuke Takahashi, Toshiyuki Watanabe, Takashi Atsumi, Junichi Nakamura, Yukiharu Hasegawa, Koichi Akashi, Ichiei Narita, Takeshi Miyamoto, Tsutomu Takeuchi, Katsunori Ikari, Koichi Amano, Atsuhiro Fujie, Toshikazu Kubo, Yoshifumi Tada, Ayumi Kaneuji, Hiroaki Nakamura, Tomoya MiyamuraTamon Kabata, Ken Yamaji, Takahiro Okawa, Akihiro Sudo, Kenji Ohzono, Yoshiya Tanaka, Yuji Yasunaga, Shuichi Matsuda, Yuuki Imai, Yasuharu Nakashima, Goro Motomura, Satoshi Ikemura, Ryosuke Yamaguchi, Kazuyuki Karasuyama, Kazuhiko Sonoda, Takashi Nishii, Takashi Sakai, Masaki Takao, Tohru Irie, Tsuyoshi Asano, Norimasa Iwasaki, Tatsuya Atsumi, Satoshi Tamaoki, Ryosuke Nakanishi, Satoe Tanabe, Shunji Kishida, Shigeo Hagiwara, Taisuke Seki, Hiroshi Tsukamoto, Hiroaki Niiro, Yojiro Arinobu, Mitsuteru Akahoshi, Hiroshi Mitoma, Masahiro Ayano, Takeshi Kuroda, Yoshiaki Toyama, Atsushi Funayama, Hironari Hanaoka, Kunihiro Yamaoka, Yasushi Kawaguchi, Hisashi Yamanaka, Tetsuji Hosozawa, Shigeki Momohara, Kentaro Chino, Mikihiro Fujioka, Keichiro Ueshima, Masashi Ishida, Masazumi Saito, Shigeki Hayashi, Akira Ikegami, Toru Ichiseki, Shigekazu Mizokawa, Yoichi Ohta, Yoshitomo Kajino, Fumio Sekiya, Fujio Higuchi, Masahiro Hasegawa, Noriki Miyamoto, Shinichi Miyazaki, Toshio Yamaguchi, Wataru Ando, Kazuyoshi Saito, Kazuhisa Nakano, Yutaka Kuroda, Takuma Yamasaki, Masato Akiyama, Michiaki Kubo, Yoichiro Kamatani, Yukihide Iwamoto, Shiro Ikegawa

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Abstract

Idiopathic osteonecrosis of the femoral head (IONFH) is an ischemic disorder that causes bone necrosis of the femoral head, resulting in hip joint dysfunction. IONFH is a polygenic disease and steroid and alcohol have already known to increase its risk; however, the mechanism of IONFH remains to be elucidated. We performed a genome-wide association study using ~60,000 subjects and found two novel loci on chromosome 20q12 and 12q24. Big data analyses identified LINC01370 as a candidate susceptibility gene in the 20q12 locus. Stratified analysis by IONFH risk factors suggested that the 12q24 locus was associated with IONFH through drinking capacity. Our findings would shed new light on pathophysiology of IONFH.

Original language	English
Article number	15035
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-14778-y
Publication status	Published - 01-12-2017

All Science Journal Classification (ASJC) codes

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10.1038/s41598-017-14778-y

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Sakamoto, Y., Yamamoto, T., Sugano, N., Takahashi, D., Watanabe, T., Atsumi, T., Nakamura, J., Hasegawa, Y., Akashi, K., Narita, I., Miyamoto, T., Takeuchi, T., Ikari, K., Amano, K., Fujie, A., Kubo, T., Tada, Y., Kaneuji, A., Nakamura, H., ... Ikegawa, S. (2017). Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head. Scientific reports, 7(1), [15035]. https://doi.org/10.1038/s41598-017-14778-y

Sakamoto, Yuma ; Yamamoto, Takuaki ; Sugano, Nobuhiko ; Takahashi, Daisuke ; Watanabe, Toshiyuki ; Atsumi, Takashi ; Nakamura, Junichi ; Hasegawa, Yukiharu ; Akashi, Koichi ; Narita, Ichiei ; Miyamoto, Takeshi ; Takeuchi, Tsutomu ; Ikari, Katsunori ; Amano, Koichi ; Fujie, Atsuhiro ; Kubo, Toshikazu ; Tada, Yoshifumi ; Kaneuji, Ayumi ; Nakamura, Hiroaki ; Miyamura, Tomoya ; Kabata, Tamon ; Yamaji, Ken ; Okawa, Takahiro ; Sudo, Akihiro ; Ohzono, Kenji ; Tanaka, Yoshiya ; Yasunaga, Yuji ; Matsuda, Shuichi ; Imai, Yuuki ; Nakashima, Yasuharu ; Motomura, Goro ; Ikemura, Satoshi ; Yamaguchi, Ryosuke ; Karasuyama, Kazuyuki ; Sonoda, Kazuhiko ; Nishii, Takashi ; Sakai, Takashi ; Takao, Masaki ; Irie, Tohru ; Asano, Tsuyoshi ; Iwasaki, Norimasa ; Atsumi, Tatsuya ; Tamaoki, Satoshi ; Nakanishi, Ryosuke ; Tanabe, Satoe ; Kishida, Shunji ; Hagiwara, Shigeo ; Seki, Taisuke ; Tsukamoto, Hiroshi ; Niiro, Hiroaki ; Arinobu, Yojiro ; Akahoshi, Mitsuteru ; Mitoma, Hiroshi ; Ayano, Masahiro ; Kuroda, Takeshi ; Toyama, Yoshiaki ; Funayama, Atsushi ; Hanaoka, Hironari ; Yamaoka, Kunihiro ; Kawaguchi, Yasushi ; Yamanaka, Hisashi ; Hosozawa, Tetsuji ; Momohara, Shigeki ; Chino, Kentaro ; Fujioka, Mikihiro ; Ueshima, Keichiro ; Ishida, Masashi ; Saito, Masazumi ; Hayashi, Shigeki ; Ikegami, Akira ; Ichiseki, Toru ; Mizokawa, Shigekazu ; Ohta, Yoichi ; Kajino, Yoshitomo ; Sekiya, Fumio ; Higuchi, Fujio ; Hasegawa, Masahiro ; Miyamoto, Noriki ; Miyazaki, Shinichi ; Yamaguchi, Toshio ; Ando, Wataru ; Saito, Kazuyoshi ; Nakano, Kazuhisa ; Kuroda, Yutaka ; Yamasaki, Takuma ; Akiyama, Masato ; Kubo, Michiaki ; Kamatani, Yoichiro ; Iwamoto, Yukihide ; Ikegawa, Shiro. / Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head. In: Scientific reports. 2017 ; Vol. 7, No. 1.

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title = "Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head",

abstract = "Idiopathic osteonecrosis of the femoral head (IONFH) is an ischemic disorder that causes bone necrosis of the femoral head, resulting in hip joint dysfunction. IONFH is a polygenic disease and steroid and alcohol have already known to increase its risk; however, the mechanism of IONFH remains to be elucidated. We performed a genome-wide association study using ~60,000 subjects and found two novel loci on chromosome 20q12 and 12q24. Big data analyses identified LINC01370 as a candidate susceptibility gene in the 20q12 locus. Stratified analysis by IONFH risk factors suggested that the 12q24 locus was associated with IONFH through drinking capacity. Our findings would shed new light on pathophysiology of IONFH.",

author = "Yuma Sakamoto and Takuaki Yamamoto and Nobuhiko Sugano and Daisuke Takahashi and Toshiyuki Watanabe and Takashi Atsumi and Junichi Nakamura and Yukiharu Hasegawa and Koichi Akashi and Ichiei Narita and Takeshi Miyamoto and Tsutomu Takeuchi and Katsunori Ikari and Koichi Amano and Atsuhiro Fujie and Toshikazu Kubo and Yoshifumi Tada and Ayumi Kaneuji and Hiroaki Nakamura and Tomoya Miyamura and Tamon Kabata and Ken Yamaji and Takahiro Okawa and Akihiro Sudo and Kenji Ohzono and Yoshiya Tanaka and Yuji Yasunaga and Shuichi Matsuda and Yuuki Imai and Yasuharu Nakashima and Goro Motomura and Satoshi Ikemura and Ryosuke Yamaguchi and Kazuyuki Karasuyama and Kazuhiko Sonoda and Takashi Nishii and Takashi Sakai and Masaki Takao and Tohru Irie and Tsuyoshi Asano and Norimasa Iwasaki and Tatsuya Atsumi and Satoshi Tamaoki and Ryosuke Nakanishi and Satoe Tanabe and Shunji Kishida and Shigeo Hagiwara and Taisuke Seki and Hiroshi Tsukamoto and Hiroaki Niiro and Yojiro Arinobu and Mitsuteru Akahoshi and Hiroshi Mitoma and Masahiro Ayano and Takeshi Kuroda and Yoshiaki Toyama and Atsushi Funayama and Hironari Hanaoka and Kunihiro Yamaoka and Yasushi Kawaguchi and Hisashi Yamanaka and Tetsuji Hosozawa and Shigeki Momohara and Kentaro Chino and Mikihiro Fujioka and Keichiro Ueshima and Masashi Ishida and Masazumi Saito and Shigeki Hayashi and Akira Ikegami and Toru Ichiseki and Shigekazu Mizokawa and Yoichi Ohta and Yoshitomo Kajino and Fumio Sekiya and Fujio Higuchi and Masahiro Hasegawa and Noriki Miyamoto and Shinichi Miyazaki and Toshio Yamaguchi and Wataru Ando and Kazuyoshi Saito and Kazuhisa Nakano and Yutaka Kuroda and Takuma Yamasaki and Masato Akiyama and Michiaki Kubo and Yoichiro Kamatani and Yukihide Iwamoto and Shiro Ikegawa",

note = "Funding Information: We thank the patients for their cooperation. This study was supported in part by the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and development, AMED, by RIKEN Junior Research Associate Program (for Y.S.), and by Grant of Japan Orthopaedics and Traumatology Research Foundation, Inc, No. 350 (for Y.S.). The study sponsors had no involvement in this study.",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41598-017-14778-y",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Sakamoto, Y, Yamamoto, T, Sugano, N, Takahashi, D, Watanabe, T, Atsumi, T, Nakamura, J, Hasegawa, Y, Akashi, K, Narita, I, Miyamoto, T, Takeuchi, T, Ikari, K, Amano, K, Fujie, A, Kubo, T, Tada, Y, Kaneuji, A, Nakamura, H, Miyamura, T, Kabata, T, Yamaji, K, Okawa, T, Sudo, A, Ohzono, K, Tanaka, Y, Yasunaga, Y, Matsuda, S, Imai, Y, Nakashima, Y, Motomura, G, Ikemura, S, Yamaguchi, R, Karasuyama, K, Sonoda, K, Nishii, T, Sakai, T, Takao, M, Irie, T, Asano, T, Iwasaki, N, Atsumi, T, Tamaoki, S, Nakanishi, R, Tanabe, S, Kishida, S, Hagiwara, S, Seki, T, Tsukamoto, H, Niiro, H, Arinobu, Y, Akahoshi, M, Mitoma, H, Ayano, M, Kuroda, T, Toyama, Y, Funayama, A, Hanaoka, H, Yamaoka, K, Kawaguchi, Y, Yamanaka, H, Hosozawa, T, Momohara, S, Chino, K, Fujioka, M, Ueshima, K, Ishida, M, Saito, M, Hayashi, S, Ikegami, A, Ichiseki, T, Mizokawa, S, Ohta, Y, Kajino, Y, Sekiya, F, Higuchi, F, Hasegawa, M, Miyamoto, N, Miyazaki, S, Yamaguchi, T, Ando, W, Saito, K, Nakano, K, Kuroda, Y, Yamasaki, T, Akiyama, M, Kubo, M, Kamatani, Y, Iwamoto, Y & Ikegawa, S 2017, 'Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head', Scientific reports, vol. 7, no. 1, 15035. https://doi.org/10.1038/s41598-017-14778-y

Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head. / Sakamoto, Yuma; Yamamoto, Takuaki; Sugano, Nobuhiko; Takahashi, Daisuke; Watanabe, Toshiyuki; Atsumi, Takashi; Nakamura, Junichi; Hasegawa, Yukiharu; Akashi, Koichi; Narita, Ichiei; Miyamoto, Takeshi; Takeuchi, Tsutomu; Ikari, Katsunori; Amano, Koichi; Fujie, Atsuhiro; Kubo, Toshikazu; Tada, Yoshifumi; Kaneuji, Ayumi; Nakamura, Hiroaki; Miyamura, Tomoya; Kabata, Tamon; Yamaji, Ken; Okawa, Takahiro; Sudo, Akihiro; Ohzono, Kenji; Tanaka, Yoshiya; Yasunaga, Yuji; Matsuda, Shuichi; Imai, Yuuki; Nakashima, Yasuharu; Motomura, Goro; Ikemura, Satoshi; Yamaguchi, Ryosuke; Karasuyama, Kazuyuki; Sonoda, Kazuhiko; Nishii, Takashi; Sakai, Takashi; Takao, Masaki; Irie, Tohru; Asano, Tsuyoshi; Iwasaki, Norimasa; Atsumi, Tatsuya; Tamaoki, Satoshi; Nakanishi, Ryosuke; Tanabe, Satoe; Kishida, Shunji; Hagiwara, Shigeo; Seki, Taisuke; Tsukamoto, Hiroshi; Niiro, Hiroaki; Arinobu, Yojiro; Akahoshi, Mitsuteru; Mitoma, Hiroshi; Ayano, Masahiro; Kuroda, Takeshi; Toyama, Yoshiaki; Funayama, Atsushi; Hanaoka, Hironari; Yamaoka, Kunihiro; Kawaguchi, Yasushi; Yamanaka, Hisashi; Hosozawa, Tetsuji; Momohara, Shigeki; Chino, Kentaro; Fujioka, Mikihiro; Ueshima, Keichiro; Ishida, Masashi; Saito, Masazumi; Hayashi, Shigeki; Ikegami, Akira; Ichiseki, Toru; Mizokawa, Shigekazu; Ohta, Yoichi; Kajino, Yoshitomo; Sekiya, Fumio; Higuchi, Fujio; Hasegawa, Masahiro; Miyamoto, Noriki; Miyazaki, Shinichi; Yamaguchi, Toshio; Ando, Wataru; Saito, Kazuyoshi; Nakano, Kazuhisa; Kuroda, Yutaka; Yamasaki, Takuma; Akiyama, Masato; Kubo, Michiaki; Kamatani, Yoichiro; Iwamoto, Yukihide; Ikegawa, Shiro.

In: Scientific reports, Vol. 7, No. 1, 15035, 01.12.2017.

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

TY - JOUR

T1 - Genome-wide Association Study of Idiopathic Osteonecrosis of the Femoral Head

AU - Sakamoto, Yuma

AU - Yamamoto, Takuaki

AU - Sugano, Nobuhiko

AU - Takahashi, Daisuke

AU - Watanabe, Toshiyuki

AU - Atsumi, Takashi

AU - Nakamura, Junichi

AU - Hasegawa, Yukiharu

AU - Akashi, Koichi

AU - Narita, Ichiei

AU - Miyamoto, Takeshi

AU - Takeuchi, Tsutomu

AU - Ikari, Katsunori

AU - Amano, Koichi

AU - Fujie, Atsuhiro

AU - Kubo, Toshikazu

AU - Tada, Yoshifumi

AU - Kaneuji, Ayumi

AU - Nakamura, Hiroaki

AU - Miyamura, Tomoya

AU - Kabata, Tamon

AU - Yamaji, Ken

AU - Okawa, Takahiro

AU - Sudo, Akihiro

AU - Ohzono, Kenji

AU - Tanaka, Yoshiya

AU - Yasunaga, Yuji

AU - Matsuda, Shuichi

AU - Imai, Yuuki

AU - Nakashima, Yasuharu

AU - Motomura, Goro

AU - Ikemura, Satoshi

AU - Yamaguchi, Ryosuke

AU - Karasuyama, Kazuyuki

AU - Sonoda, Kazuhiko

AU - Nishii, Takashi

AU - Sakai, Takashi

AU - Takao, Masaki

AU - Irie, Tohru

AU - Asano, Tsuyoshi

AU - Iwasaki, Norimasa

AU - Atsumi, Tatsuya

AU - Tamaoki, Satoshi

AU - Nakanishi, Ryosuke

AU - Tanabe, Satoe

AU - Kishida, Shunji

AU - Hagiwara, Shigeo

AU - Seki, Taisuke

AU - Tsukamoto, Hiroshi

AU - Niiro, Hiroaki

AU - Arinobu, Yojiro

AU - Akahoshi, Mitsuteru

AU - Mitoma, Hiroshi

AU - Ayano, Masahiro

AU - Kuroda, Takeshi

AU - Toyama, Yoshiaki

AU - Funayama, Atsushi

AU - Hanaoka, Hironari

AU - Yamaoka, Kunihiro

AU - Kawaguchi, Yasushi

AU - Yamanaka, Hisashi

AU - Hosozawa, Tetsuji

AU - Momohara, Shigeki

AU - Chino, Kentaro

AU - Fujioka, Mikihiro

AU - Ueshima, Keichiro

AU - Ishida, Masashi

AU - Saito, Masazumi

AU - Hayashi, Shigeki

AU - Ikegami, Akira

AU - Ichiseki, Toru

AU - Mizokawa, Shigekazu

AU - Ohta, Yoichi

AU - Kajino, Yoshitomo

AU - Sekiya, Fumio

AU - Higuchi, Fujio

AU - Hasegawa, Masahiro

AU - Miyamoto, Noriki

AU - Miyazaki, Shinichi

AU - Yamaguchi, Toshio

AU - Ando, Wataru

AU - Saito, Kazuyoshi

AU - Nakano, Kazuhisa

AU - Kuroda, Yutaka

AU - Yamasaki, Takuma

AU - Akiyama, Masato

AU - Kubo, Michiaki

AU - Kamatani, Yoichiro

AU - Iwamoto, Yukihide

AU - Ikegawa, Shiro

N1 - Funding Information: We thank the patients for their cooperation. This study was supported in part by the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and development, AMED, by RIKEN Junior Research Associate Program (for Y.S.), and by Grant of Japan Orthopaedics and Traumatology Research Foundation, Inc, No. 350 (for Y.S.). The study sponsors had no involvement in this study.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Idiopathic osteonecrosis of the femoral head (IONFH) is an ischemic disorder that causes bone necrosis of the femoral head, resulting in hip joint dysfunction. IONFH is a polygenic disease and steroid and alcohol have already known to increase its risk; however, the mechanism of IONFH remains to be elucidated. We performed a genome-wide association study using ~60,000 subjects and found two novel loci on chromosome 20q12 and 12q24. Big data analyses identified LINC01370 as a candidate susceptibility gene in the 20q12 locus. Stratified analysis by IONFH risk factors suggested that the 12q24 locus was associated with IONFH through drinking capacity. Our findings would shed new light on pathophysiology of IONFH.

AB - Idiopathic osteonecrosis of the femoral head (IONFH) is an ischemic disorder that causes bone necrosis of the femoral head, resulting in hip joint dysfunction. IONFH is a polygenic disease and steroid and alcohol have already known to increase its risk; however, the mechanism of IONFH remains to be elucidated. We performed a genome-wide association study using ~60,000 subjects and found two novel loci on chromosome 20q12 and 12q24. Big data analyses identified LINC01370 as a candidate susceptibility gene in the 20q12 locus. Stratified analysis by IONFH risk factors suggested that the 12q24 locus was associated with IONFH through drinking capacity. Our findings would shed new light on pathophysiology of IONFH.

UR - http://www.scopus.com/inward/record.url?scp=85033388373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033388373&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-14778-y

DO - 10.1038/s41598-017-14778-y

M3 - Article

AN - SCOPUS:85033388373

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 15035

ER -