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DOCK2 is involved in the host genetics and biology of severe COVID-19
Nature ( IF 50.5 ) Pub Date : 2022-08-08 , DOI: 10.1038/s41586-022-05163-5 Ho Namkoong 1 , Ryuya Edahiro 2, 3 , Tomomi Takano 4 , Hiroshi Nishihara 5 , Yuya Shirai 2, 3 , Kyuto Sonehara 2, 6 , Hiromu Tanaka 7 , Shuhei Azekawa 7 , Yohei Mikami 8 , Ho Lee 7 , Takanori Hasegawa 9 , Koji Okudela 10 , Daisuke Okuzaki 11 , Daisuke Motooka 12 , Masahiro Kanai 13 , Tatsuhiko Naito 2 , Kenichi Yamamoto 2 , Qingbo S Wang 2 , Ryunosuke Saiki 14 , Rino Ishihara 8 , Yuta Matsubara 8 , Junko Hamamoto 7 , Hiroyuki Hayashi 15 , Yukihiro Yoshimura 16 , Natsuo Tachikawa 16 , Emmy Yanagita 5 , Takayoshi Hyugaji 17 , Eigo Shimizu 17 , Kotoe Katayama 17 , Yasuhiro Kato 3, 18 , Takayoshi Morita 3, 18 , Kazuhisa Takahashi 19 , Norihiro Harada 19 , Toshio Naito 20 , Makoto Hiki 21, 22 , Yasushi Matsushita 23 , Haruhi Takagi 19 , Ryousuke Aoki 24 , Ai Nakamura 19 , Sonoko Harada 19, 25 , Hitoshi Sasano 19 , Hiroki Kabata 7 , Katsunori Masaki 7 , Hirofumi Kamata 7 , Shinnosuke Ikemura 7 , Shotaro Chubachi 7 , Satoshi Okamori 7 , Hideki Terai 7 , Atsuho Morita 7 , Takanori Asakura 7 , Junichi Sasaki 26 , Hiroshi Morisaki 27 , Yoshifumi Uwamino 28 , Kosaku Nanki 8 , Sho Uchida 1 , Shunsuke Uno 1 , Tomoyasu Nishimura 1, 29 , Takashi Ishiguro 30 , Taisuke Isono 30 , Shun Shibata 30 , Yuma Matsui 30 , Chiaki Hosoda 30 , Kenji Takano 30 , Takashi Nishida 30 , Yoichi Kobayashi 30 , Yotaro Takaku 30 , Noboru Takayanagi 30 , Soichiro Ueda 31 , Ai Tada 31 , Masayoshi Miyawaki 31 , Masaomi Yamamoto 31 , Eriko Yoshida 31 , Reina Hayashi 31 , Tomoki Nagasaka 31 , Sawako Arai 31 , Yutaro Kaneko 31 , Kana Sasaki 31 , Etsuko Tagaya 32 , Masatoshi Kawana 33 , Ken Arimura 32 , Kunihiko Takahashi 9 , Tatsuhiko Anzai 9 , Satoshi Ito 9 , Akifumi Endo 34 , Yuji Uchimura 35 , Yasunari Miyazaki 36 , Takayuki Honda 36 , Tomoya Tateishi 36 , Shuji Tohda 37 , Naoya Ichimura 37 , Kazunari Sonobe 37 , Chihiro Tani Sassa 37 , Jun Nakajima 37 , Yasushi Nakano 38 , Yukiko Nakajima 38 , Ryusuke Anan 38 , Ryosuke Arai 38 , Yuko Kurihara 38 , Yuko Harada 38 , Kazumi Nishio 38 , Tetsuya Ueda 39 , Masanori Azuma 39 , Ryuichi Saito 39 , Toshikatsu Sado 39 , Yoshimune Miyazaki 39 , Ryuichi Sato 39 , Yuki Haruta 39 , Tadao Nagasaki 39 , Yoshinori Yasui 40 , Yoshinori Hasegawa 39 , Yoshikazu Mutoh 41 , Tomoki Kimura 42 , Tomonori Sato 42 , Reoto Takei 42 , Satoshi Hagimoto 42 , Yoichiro Noguchi 42 , Yasuhiko Yamano 42 , Hajime Sasano 42 , Sho Ota 42 , Yasushi Nakamori 43 , Kazuhisa Yoshiya 43 , Fukuki Saito 43 , Tomoyuki Yoshihara 43 , Daiki Wada 43 , Hiromu Iwamura 43 , Syuji Kanayama 43 , Shuhei Maruyama 43 , Takashi Yoshiyama 44 , Ken Ohta 44 , Hiroyuki Kokuto 44 , Hideo Ogata 44 , Yoshiaki Tanaka 44 , Kenichi Arakawa 44 , Masafumi Shimoda 44 , Takeshi Osawa 44 , Hiroki Tateno 45 , Isano Hase 45 , Shuichi Yoshida 45 , Shoji Suzuki 45 , Miki Kawada 46 , Hirohisa Horinouchi 47 , Fumitake Saito 48 , Keiko Mitamura 49 , Masao Hagihara 50 , Junichi Ochi 48 , Tomoyuki Uchida 50 , Rie Baba 51 , Daisuke Arai 51 , Takayuki Ogura 51 , Hidenori Takahashi 51 , Shigehiro Hagiwara 51 , Genta Nagao 51 , Shunichiro Konishi 51 , Ichiro Nakachi 51 , Koji Murakami 52 , Mitsuhiro Yamada 52 , Hisatoshi Sugiura 52 , Hirohito Sano 52 , Shuichiro Matsumoto 52 , Nozomu Kimura 52 , Yoshinao Ono 52 , Hiroaki Baba 53 , Yusuke Suzuki 54 , Sohei Nakayama 54 , Keita Masuzawa 54 , Shinichi Namba 2 , Ken Suzuki 2 , Yoko Naito 12 , Yu-Chen Liu 11 , Ayako Takuwa 11 , Fuminori Sugihara 55 , James B Wing 56, 57 , Shuhei Sakakibara 58 , Nobuyuki Hizawa 59 , Takayuki Shiroyama 3 , Satoru Miyawaki 60 , Yusuke Kawamura 61 , Akiyoshi Nakayama 61 , Hirotaka Matsuo 61 , Yuichi Maeda 3 , Takuro Nii 3 , Yoshimi Noda 3 , Takayuki Niitsu 3 , Yuichi Adachi 3 , Takatoshi Enomoto 3 , Saori Amiya 3 , Reina Hara 3 , Yuta Yamaguchi 3, 18 , Teruaki Murakami 3, 18 , Tomoki Kuge 3 , Kinnosuke Matsumoto 3 , Yuji Yamamoto 3 , Makoto Yamamoto 3 , Midori Yoneda 3 , Toshihiro Kishikawa 2, 62, 63 , Shuhei Yamada 64 , Shuhei Kawabata 64 , Noriyuki Kijima 64 , Masatoshi Takagaki 64 , Noah Sasa 2, 62 , Yuya Ueno 62 , Motoyuki Suzuki 62 , Norihiko Takemoto 62 , Hirotaka Eguchi 62 , Takahito Fukusumi 62 , Takao Imai 62 , Munehisa Fukushima 62, 65 , Haruhiko Kishima 64 , Hidenori Inohara 62 , Kazunori Tomono 66 , Kazuto Kato 67 , Meiko Takahashi 68 , Fumihiko Matsuda 68 , Haruhiko Hirata 3 , Yoshito Takeda 3 , Hidefumi Koh 69 , Tadashi Manabe 69 , Yohei Funatsu 69 , Fumimaro Ito 69 , Takahiro Fukui 69 , Keisuke Shinozuka 69 , Sumiko Kohashi 69 , Masatoshi Miyazaki 69 , Tomohisa Shoko 70 , Mitsuaki Kojima 70 , Tomohiro Adachi 70 , Motonao Ishikawa 71 , Kenichiro Takahashi 72 , Takashi Inoue 73 , Toshiyuki Hirano 73 , Keigo Kobayashi 73 , Hatsuyo Takaoka 73 , Kazuyoshi Watanabe 74 , Naoki Miyazawa 75 , Yasuhiro Kimura 75 , Reiko Sado 75 , Hideyasu Sugimoto 75 , Akane Kamiya 76 , Naota Kuwahara 77 , Akiko Fujiwara 77 , Tomohiro Matsunaga 77 , Yoko Sato 77 , Takenori Okada 77 , Yoshihiro Hirai 78 , Hidetoshi Kawashima 78 , Atsuya Narita 78 , Kazuki Niwa 79 , Yoshiyuki Sekikawa 79 , Koichi Nishi 80 , Masaru Nishitsuji 80 , Mayuko Tani 80 , Junya Suzuki 80 , Hiroki Nakatsumi 80 , Takashi Ogura 81 , Hideya Kitamura 81 , Eri Hagiwara 81 , Kota Murohashi 81 , Hiroko Okabayashi 81 , Takao Mochimaru 82, 83 , Shigenari Nukaga 82 , Ryosuke Satomi 82 , Yoshitaka Oyamada 82, 83 , Nobuaki Mori 84 , Tomoya Baba 85 , Yasutaka Fukui 85 , Mitsuru Odate 85 , Shuko Mashimo 85 , Yasushi Makino 85 , Kazuma Yagi 86 , Mizuha Hashiguchi 86 , Junko Kagyo 86 , Tetsuya Shiomi 86 , Satoshi Fuke 87 , Hiroshi Saito 87 , Tomoya Tsuchida 88 , Shigeki Fujitani 89 , Mumon Takita 89 , Daiki Morikawa 89 , Toru Yoshida 89 , Takehiro Izumo 90 , Minoru Inomata 90 , Naoyuki Kuse 90 , Nobuyasu Awano 90 , Mari Tone 90 , Akihiro Ito 91 , Yoshihiko Nakamura 92 , Kota Hoshino 92 , Junichi Maruyama 92 , Hiroyasu Ishikura 92 , Tohru Takata 93 , Toshio Odani 94 , Masaru Amishima 95 , Takeshi Hattori 95 , Yasuo Shichinohe 96 , Takashi Kagaya 97 , Toshiyuki Kita 97 , Kazuhide Ohta 97 , Satoru Sakagami 97 , Kiyoshi Koshida 97 , Kentaro Hayashi 98 , Tetsuo Shimizu 98 , Yutaka Kozu 98 , Hisato Hiranuma 98 , Yasuhiro Gon 98 , Namiki Izumi 99 , Kaoru Nagata 99 , Ken Ueda 99 , Reiko Taki 99 , Satoko Hanada 99 , Kodai Kawamura 100 , Kazuya Ichikado 100 , Kenta Nishiyama 100 , Hiroyuki Muranaka 100 , Kazunori Nakamura 100 , Naozumi Hashimoto 101 , Keiko Wakahara 101 , Koji Sakamoto 101 , Norihito Omote 101 , Akira Ando 101 , Nobuhiro Kodama 102 , Yasunari Kaneyama 102 , Shunsuke Maeda 102 , Takashige Kuraki 103 , Takemasa Matsumoto 103 , Koutaro Yokote 104 , Taka-Aki Nakada 105 , Ryuzo Abe 105 , Taku Oshima 105 , Tadanaga Shimada 105 , Masahiro Harada 106 , Takeshi Takahashi 106 , Hiroshi Ono 106 , Toshihiro Sakurai 106 , Takayuki Shibusawa 106 , Yoshifumi Kimizuka 107 , Akihiko Kawana 107 , Tomoya Sano 107 , Chie Watanabe 107 , Ryohei Suematsu 107 , Hisako Sageshima 108 , Ayumi Yoshifuji 109 , Kazuto Ito 109 , Saeko Takahashi 110 , Kota Ishioka 110 , Morio Nakamura 110 , Makoto Masuda 111 , Aya Wakabayashi 111 , Hiroki Watanabe 111 , Suguru Ueda 111 , Masanori Nishikawa 111 , Yusuke Chihara 112 , Mayumi Takeuchi 112 , Keisuke Onoi 112 , Jun Shinozuka 112 , Atsushi Sueyoshi 112 , Yoji Nagasaki 113 , Masaki Okamoto 114, 115 , Sayoko Ishihara 116 , Masatoshi Shimo 116 , Yoshihisa Tokunaga 114, 115 , Yu Kusaka 117 , Takehiko Ohba 117 , Susumu Isogai 117 , Aki Ogawa 117 , Takuya Inoue 117 , Satoru Fukuyama 118 , Yoshihiro Eriguchi 119 , Akiko Yonekawa 119 , Keiko Kan-O 118 , Koichiro Matsumoto 118 , Kensuke Kanaoka 120 , Shoichi Ihara 120 , Kiyoshi Komuta 120 , Yoshiaki Inoue 121 , Shigeru Chiba 122 , Kunihiro Yamagata 123 , Yuji Hiramatsu 124 , Hirayasu Kai 123 , Koichiro Asano 125 , Tsuyoshi Oguma 125 , Yoko Ito 125 , Satoru Hashimoto 126 , Masaki Yamasaki 126 , Yu Kasamatsu 127 , Yuko Komase 128 , Naoya Hida 128 , Takahiro Tsuburai 128 , Baku Oyama 128 , Minoru Takada 129 , Hidenori Kanda 129 , Yuichiro Kitagawa 130 , Tetsuya Fukuta 130 , Takahito Miyake 130 , Shozo Yoshida 130 , Shinji Ogura 130 , Shinji Abe 131 , Yuta Kono 131 , Yuki Togashi 131 , Hiroyuki Takoi 131 , Ryota Kikuchi 131 , Shinichi Ogawa 132 , Tomouki Ogata 132 , Shoichiro Ishihara 132 , Arihiko Kanehiro 133, 134 , Shinji Ozaki 133 , Yasuko Fuchimoto 133 , Sae Wada 133 , Nobukazu Fujimoto 133 , Kei Nishiyama 135 , Mariko Terashima 136 , Satoru Beppu 136 , Kosuke Yoshida 136 , Osamu Narumoto 137 , Hideaki Nagai 137 , Nobuharu Ooshima 137 , Mitsuru Motegi 138 , Akira Umeda 139 , Kazuya Miyagawa 140 , Hisato Shimada 141 , Mayu Endo 142 , Yoshiyuki Ohira 139 , Masafumi Watanabe 143 , Sumito Inoue 143 , Akira Igarashi 143 , Masamichi Sato 143 , Hironori Sagara 144 , Akihiko Tanaka 144 , Shin Ohta 144 , Tomoyuki Kimura 144 , Yoko Shibata 145 , Yoshinori Tanino 145 , Takefumi Nikaido 145 , Hiroyuki Minemura 145 , Yuki Sato 145 , Yuichiro Yamada 146 , Takuya Hashino 146 , Masato Shinoki 146 , Hajime Iwagoe 147 , Hiroshi Takahashi 148 , Kazuhiko Fujii 148 , Hiroto Kishi 148 , Masayuki Kanai 149 , Tomonori Imamura 149 , Tatsuya Yamashita 149 , Masakiyo Yatomi 150 , Toshitaka Maeno 150 , Shinichi Hayashi 151 , Mai Takahashi 151 , Mizuki Kuramochi 151 , Isamu Kamimaki 151 , Yoshiteru Tominaga 151 , Tomoo Ishii 152 , Mitsuyoshi Utsugi 153 , Akihiro Ono 153 , Toru Tanaka 154 , Takeru Kashiwada 154 , Kazue Fujita 154 , Yoshinobu Saito 154 , Masahiro Seike 154 , Hiroko Watanabe 155 , Hiroto Matsuse 156 , Norio Kodaka 156 , Chihiro Nakano 156 , Takeshi Oshio 156 , Takatomo Hirouchi 156 , Shohei Makino 157 , Moritoki Egi 157 , , Yosuke Omae 158 , Yasuhito Nannya 14 , Takafumi Ueno 159 , Kazuhiko Katayama 160 , Masumi Ai 161 , Yoshinori Fukui 162 , Atsushi Kumanogoh 3, 6, 18, 57 , Toshiro Sato 163 , Naoki Hasegawa 1 , Katsushi Tokunaga 158 , Makoto Ishii 7 , Ryuji Koike 164 , Yuko Kitagawa 165 , Akinori Kimura 166 , Seiya Imoto 17 , Satoru Miyano 9 , Seishi Ogawa 14, 167, 168 , Takanori Kanai 8, 169 , Koichi Fukunaga 7 , Yukinori Okada 2, 6, 57, 170, 171, 172
中文翻译：
DOCK2 参与重症 COVID-19 的宿主遗传学和生物学
更新日期：2022-08-08
Nature ( IF 50.5 ) Pub Date : 2022-08-08 , DOI: 10.1038/s41586-022-05163-5 Ho Namkoong 1 , Ryuya Edahiro 2, 3 , Tomomi Takano 4 , Hiroshi Nishihara 5 , Yuya Shirai 2, 3 , Kyuto Sonehara 2, 6 , Hiromu Tanaka 7 , Shuhei Azekawa 7 , Yohei Mikami 8 , Ho Lee 7 , Takanori Hasegawa 9 , Koji Okudela 10 , Daisuke Okuzaki 11 , Daisuke Motooka 12 , Masahiro Kanai 13 , Tatsuhiko Naito 2 , Kenichi Yamamoto 2 , Qingbo S Wang 2 , Ryunosuke Saiki 14 , Rino Ishihara 8 , Yuta Matsubara 8 , Junko Hamamoto 7 , Hiroyuki Hayashi 15 , Yukihiro Yoshimura 16 , Natsuo Tachikawa 16 , Emmy Yanagita 5 , Takayoshi Hyugaji 17 , Eigo Shimizu 17 , Kotoe Katayama 17 , Yasuhiro Kato 3, 18 , Takayoshi Morita 3, 18 , Kazuhisa Takahashi 19 , Norihiro Harada 19 , Toshio Naito 20 , Makoto Hiki 21, 22 , Yasushi Matsushita 23 , Haruhi Takagi 19 , Ryousuke Aoki 24 , Ai Nakamura 19 , Sonoko Harada 19, 25 , Hitoshi Sasano 19 , Hiroki Kabata 7 , Katsunori Masaki 7 , Hirofumi Kamata 7 , Shinnosuke Ikemura 7 , Shotaro Chubachi 7 , Satoshi Okamori 7 , Hideki Terai 7 , Atsuho Morita 7 , Takanori Asakura 7 , Junichi Sasaki 26 , Hiroshi Morisaki 27 , Yoshifumi Uwamino 28 , Kosaku Nanki 8 , Sho Uchida 1 , Shunsuke Uno 1 , Tomoyasu Nishimura 1, 29 , Takashi Ishiguro 30 , Taisuke Isono 30 , Shun Shibata 30 , Yuma Matsui 30 , Chiaki Hosoda 30 , Kenji Takano 30 , Takashi Nishida 30 , Yoichi Kobayashi 30 , Yotaro Takaku 30 , Noboru Takayanagi 30 , Soichiro Ueda 31 , Ai Tada 31 , Masayoshi Miyawaki 31 , Masaomi Yamamoto 31 , Eriko Yoshida 31 , Reina Hayashi 31 , Tomoki Nagasaka 31 , Sawako Arai 31 , Yutaro Kaneko 31 , Kana Sasaki 31 , Etsuko Tagaya 32 , Masatoshi Kawana 33 , Ken Arimura 32 , Kunihiko Takahashi 9 , Tatsuhiko Anzai 9 , Satoshi Ito 9 , Akifumi Endo 34 , Yuji Uchimura 35 , Yasunari Miyazaki 36 , Takayuki Honda 36 , Tomoya Tateishi 36 , Shuji Tohda 37 , Naoya Ichimura 37 , Kazunari Sonobe 37 , Chihiro Tani Sassa 37 , Jun Nakajima 37 , Yasushi Nakano 38 , Yukiko Nakajima 38 , Ryusuke Anan 38 , Ryosuke Arai 38 , Yuko Kurihara 38 , Yuko Harada 38 , Kazumi Nishio 38 , Tetsuya Ueda 39 , Masanori Azuma 39 , Ryuichi Saito 39 , Toshikatsu Sado 39 , Yoshimune Miyazaki 39 , Ryuichi Sato 39 , Yuki Haruta 39 , Tadao Nagasaki 39 , Yoshinori Yasui 40 , Yoshinori Hasegawa 39 , Yoshikazu Mutoh 41 , Tomoki Kimura 42 , Tomonori Sato 42 , Reoto Takei 42 , Satoshi Hagimoto 42 , Yoichiro Noguchi 42 , Yasuhiko Yamano 42 , Hajime Sasano 42 , Sho Ota 42 , Yasushi Nakamori 43 , Kazuhisa Yoshiya 43 , Fukuki Saito 43 , Tomoyuki Yoshihara 43 , Daiki Wada 43 , Hiromu Iwamura 43 , Syuji Kanayama 43 , Shuhei Maruyama 43 , Takashi Yoshiyama 44 , Ken Ohta 44 , Hiroyuki Kokuto 44 , Hideo Ogata 44 , Yoshiaki Tanaka 44 , Kenichi Arakawa 44 , Masafumi Shimoda 44 , Takeshi Osawa 44 , Hiroki Tateno 45 , Isano Hase 45 , Shuichi Yoshida 45 , Shoji Suzuki 45 , Miki Kawada 46 , Hirohisa Horinouchi 47 , Fumitake Saito 48 , Keiko Mitamura 49 , Masao Hagihara 50 , Junichi Ochi 48 , Tomoyuki Uchida 50 , Rie Baba 51 , Daisuke Arai 51 , Takayuki Ogura 51 , Hidenori Takahashi 51 , Shigehiro Hagiwara 51 , Genta Nagao 51 , Shunichiro Konishi 51 , Ichiro Nakachi 51 , Koji Murakami 52 , Mitsuhiro Yamada 52 , Hisatoshi Sugiura 52 , Hirohito Sano 52 , Shuichiro Matsumoto 52 , Nozomu Kimura 52 , Yoshinao Ono 52 , Hiroaki Baba 53 , Yusuke Suzuki 54 , Sohei Nakayama 54 , Keita Masuzawa 54 , Shinichi Namba 2 , Ken Suzuki 2 , Yoko Naito 12 , Yu-Chen Liu 11 , Ayako Takuwa 11 , Fuminori Sugihara 55 , James B Wing 56, 57 , Shuhei Sakakibara 58 , Nobuyuki Hizawa 59 , Takayuki Shiroyama 3 , Satoru Miyawaki 60 , Yusuke Kawamura 61 , Akiyoshi Nakayama 61 , Hirotaka Matsuo 61 , Yuichi Maeda 3 , Takuro Nii 3 , Yoshimi Noda 3 , Takayuki Niitsu 3 , Yuichi Adachi 3 , Takatoshi Enomoto 3 , Saori Amiya 3 , Reina Hara 3 , Yuta Yamaguchi 3, 18 , Teruaki Murakami 3, 18 , Tomoki Kuge 3 , Kinnosuke Matsumoto 3 , Yuji Yamamoto 3 , Makoto Yamamoto 3 , Midori Yoneda 3 , Toshihiro Kishikawa 2, 62, 63 , Shuhei Yamada 64 , Shuhei Kawabata 64 , Noriyuki Kijima 64 , Masatoshi Takagaki 64 , Noah Sasa 2, 62 , Yuya Ueno 62 , Motoyuki Suzuki 62 , Norihiko Takemoto 62 , Hirotaka Eguchi 62 , Takahito Fukusumi 62 , Takao Imai 62 , Munehisa Fukushima 62, 65 , Haruhiko Kishima 64 , Hidenori Inohara 62 , Kazunori Tomono 66 , Kazuto Kato 67 , Meiko Takahashi 68 , Fumihiko Matsuda 68 , Haruhiko Hirata 3 , Yoshito Takeda 3 , Hidefumi Koh 69 , Tadashi Manabe 69 , Yohei Funatsu 69 , Fumimaro Ito 69 , Takahiro Fukui 69 , Keisuke Shinozuka 69 , Sumiko Kohashi 69 , Masatoshi Miyazaki 69 , Tomohisa Shoko 70 , Mitsuaki Kojima 70 , Tomohiro Adachi 70 , Motonao Ishikawa 71 , Kenichiro Takahashi 72 , Takashi Inoue 73 , Toshiyuki Hirano 73 , Keigo Kobayashi 73 , Hatsuyo Takaoka 73 , Kazuyoshi Watanabe 74 , Naoki Miyazawa 75 , Yasuhiro Kimura 75 , Reiko Sado 75 , Hideyasu Sugimoto 75 , Akane Kamiya 76 , Naota Kuwahara 77 , Akiko Fujiwara 77 , Tomohiro Matsunaga 77 , Yoko Sato 77 , Takenori Okada 77 , Yoshihiro Hirai 78 , Hidetoshi Kawashima 78 , Atsuya Narita 78 , Kazuki Niwa 79 , Yoshiyuki Sekikawa 79 , Koichi Nishi 80 , Masaru Nishitsuji 80 , Mayuko Tani 80 , Junya Suzuki 80 , Hiroki Nakatsumi 80 , Takashi Ogura 81 , Hideya Kitamura 81 , Eri Hagiwara 81 , Kota Murohashi 81 , Hiroko Okabayashi 81 , Takao Mochimaru 82, 83 , Shigenari Nukaga 82 , Ryosuke Satomi 82 , Yoshitaka Oyamada 82, 83 , Nobuaki Mori 84 , Tomoya Baba 85 , Yasutaka Fukui 85 , Mitsuru Odate 85 , Shuko Mashimo 85 , Yasushi Makino 85 , Kazuma Yagi 86 , Mizuha Hashiguchi 86 , Junko Kagyo 86 , Tetsuya Shiomi 86 , Satoshi Fuke 87 , Hiroshi Saito 87 , Tomoya Tsuchida 88 , Shigeki Fujitani 89 , Mumon Takita 89 , Daiki Morikawa 89 , Toru Yoshida 89 , Takehiro Izumo 90 , Minoru Inomata 90 , Naoyuki Kuse 90 , Nobuyasu Awano 90 , Mari Tone 90 , Akihiro Ito 91 , Yoshihiko Nakamura 92 , Kota Hoshino 92 , Junichi Maruyama 92 , Hiroyasu Ishikura 92 , Tohru Takata 93 , Toshio Odani 94 , Masaru Amishima 95 , Takeshi Hattori 95 , Yasuo Shichinohe 96 , Takashi Kagaya 97 , Toshiyuki Kita 97 , Kazuhide Ohta 97 , Satoru Sakagami 97 , Kiyoshi Koshida 97 , Kentaro Hayashi 98 , Tetsuo Shimizu 98 , Yutaka Kozu 98 , Hisato Hiranuma 98 , Yasuhiro Gon 98 , Namiki Izumi 99 , Kaoru Nagata 99 , Ken Ueda 99 , Reiko Taki 99 , Satoko Hanada 99 , Kodai Kawamura 100 , Kazuya Ichikado 100 , Kenta Nishiyama 100 , Hiroyuki Muranaka 100 , Kazunori Nakamura 100 , Naozumi Hashimoto 101 , Keiko Wakahara 101 , Koji Sakamoto 101 , Norihito Omote 101 , Akira Ando 101 , Nobuhiro Kodama 102 , Yasunari Kaneyama 102 , Shunsuke Maeda 102 , Takashige Kuraki 103 , Takemasa Matsumoto 103 , Koutaro Yokote 104 , Taka-Aki Nakada 105 , Ryuzo Abe 105 , Taku Oshima 105 , Tadanaga Shimada 105 , Masahiro Harada 106 , Takeshi Takahashi 106 , Hiroshi Ono 106 , Toshihiro Sakurai 106 , Takayuki Shibusawa 106 , Yoshifumi Kimizuka 107 , Akihiko Kawana 107 , Tomoya Sano 107 , Chie Watanabe 107 , Ryohei Suematsu 107 , Hisako Sageshima 108 , Ayumi Yoshifuji 109 , Kazuto Ito 109 , Saeko Takahashi 110 , Kota Ishioka 110 , Morio Nakamura 110 , Makoto Masuda 111 , Aya Wakabayashi 111 , Hiroki Watanabe 111 , Suguru Ueda 111 , Masanori Nishikawa 111 , Yusuke Chihara 112 , Mayumi Takeuchi 112 , Keisuke Onoi 112 , Jun Shinozuka 112 , Atsushi Sueyoshi 112 , Yoji Nagasaki 113 , Masaki Okamoto 114, 115 , Sayoko Ishihara 116 , Masatoshi Shimo 116 , Yoshihisa Tokunaga 114, 115 , Yu Kusaka 117 , Takehiko Ohba 117 , Susumu Isogai 117 , Aki Ogawa 117 , Takuya Inoue 117 , Satoru Fukuyama 118 , Yoshihiro Eriguchi 119 , Akiko Yonekawa 119 , Keiko Kan-O 118 , Koichiro Matsumoto 118 , Kensuke Kanaoka 120 , Shoichi Ihara 120 , Kiyoshi Komuta 120 , Yoshiaki Inoue 121 , Shigeru Chiba 122 , Kunihiro Yamagata 123 , Yuji Hiramatsu 124 , Hirayasu Kai 123 , Koichiro Asano 125 , Tsuyoshi Oguma 125 , Yoko Ito 125 , Satoru Hashimoto 126 , Masaki Yamasaki 126 , Yu Kasamatsu 127 , Yuko Komase 128 , Naoya Hida 128 , Takahiro Tsuburai 128 , Baku Oyama 128 , Minoru Takada 129 , Hidenori Kanda 129 , Yuichiro Kitagawa 130 , Tetsuya Fukuta 130 , Takahito Miyake 130 , Shozo Yoshida 130 , Shinji Ogura 130 , Shinji Abe 131 , Yuta Kono 131 , Yuki Togashi 131 , Hiroyuki Takoi 131 , Ryota Kikuchi 131 , Shinichi Ogawa 132 , Tomouki Ogata 132 , Shoichiro Ishihara 132 , Arihiko Kanehiro 133, 134 , Shinji Ozaki 133 , Yasuko Fuchimoto 133 , Sae Wada 133 , Nobukazu Fujimoto 133 , Kei Nishiyama 135 , Mariko Terashima 136 , Satoru Beppu 136 , Kosuke Yoshida 136 , Osamu Narumoto 137 , Hideaki Nagai 137 , Nobuharu Ooshima 137 , Mitsuru Motegi 138 , Akira Umeda 139 , Kazuya Miyagawa 140 , Hisato Shimada 141 , Mayu Endo 142 , Yoshiyuki Ohira 139 , Masafumi Watanabe 143 , Sumito Inoue 143 , Akira Igarashi 143 , Masamichi Sato 143 , Hironori Sagara 144 , Akihiko Tanaka 144 , Shin Ohta 144 , Tomoyuki Kimura 144 , Yoko Shibata 145 , Yoshinori Tanino 145 , Takefumi Nikaido 145 , Hiroyuki Minemura 145 , Yuki Sato 145 , Yuichiro Yamada 146 , Takuya Hashino 146 , Masato Shinoki 146 , Hajime Iwagoe 147 , Hiroshi Takahashi 148 , Kazuhiko Fujii 148 , Hiroto Kishi 148 , Masayuki Kanai 149 , Tomonori Imamura 149 , Tatsuya Yamashita 149 , Masakiyo Yatomi 150 , Toshitaka Maeno 150 , Shinichi Hayashi 151 , Mai Takahashi 151 , Mizuki Kuramochi 151 , Isamu Kamimaki 151 , Yoshiteru Tominaga 151 , Tomoo Ishii 152 , Mitsuyoshi Utsugi 153 , Akihiro Ono 153 , Toru Tanaka 154 , Takeru Kashiwada 154 , Kazue Fujita 154 , Yoshinobu Saito 154 , Masahiro Seike 154 , Hiroko Watanabe 155 , Hiroto Matsuse 156 , Norio Kodaka 156 , Chihiro Nakano 156 , Takeshi Oshio 156 , Takatomo Hirouchi 156 , Shohei Makino 157 , Moritoki Egi 157 , , Yosuke Omae 158 , Yasuhito Nannya 14 , Takafumi Ueno 159 , Kazuhiko Katayama 160 , Masumi Ai 161 , Yoshinori Fukui 162 , Atsushi Kumanogoh 3, 6, 18, 57 , Toshiro Sato 163 , Naoki Hasegawa 1 , Katsushi Tokunaga 158 , Makoto Ishii 7 , Ryuji Koike 164 , Yuko Kitagawa 165 , Akinori Kimura 166 , Seiya Imoto 17 , Satoru Miyano 9 , Seishi Ogawa 14, 167, 168 , Takanori Kanai 8, 169 , Koichi Fukunaga 7 , Yukinori Okada 2, 6, 57, 170, 171, 172
Affiliation
Identifying the factors underlying severe COVID-19 in the host genetics is an emerging issue1–5. We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls, which identified a variant on 5q35 (rs60200309-A) near DOCK2 associated with severe COVID-19 in younger (<65 ages) patients (nCase=440, odds ratio=2.01, P=1.2×10-8). This risk allele was prevalent in East Asians but rare in Europeans, showing a value of non-European GWAS. RNA-seq of 473 bulk peripheral blood identified decreasing effect of the risk allele on DOCK2 expression in younger patients. DOCK2 expression was suppressed in severe forms of COVID-19. Single cell RNA-seq analysis (n=61) identified cell type-specific downregulation of DOCK2 and COVID-19-specific decreasing effects of the risk allele on DOCK2 in non-classical monocytes. Immunohistochemistry of lung specimens from severe COVID-19 pneumonia showed suppressed DOCK2. Moreover, inhibition of DOCK2 function using CPYPP induced much more severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection characterized as weight loss, lung edema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 plays an important role in the host immune response to SARS-CoV-2 infection and development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
中文翻译：
DOCK2 参与重症 COVID-19 的宿主遗传学和生物学
确定宿主遗传学中严重 COVID-19 的潜在因素是一个新兴问题1-5。我们进行了一项全基因组关联研究 (GWAS)，涉及在最初的大流行波中收集的 2,393 例日本 COVID-19 病例和 3,289 例对照，该研究确定了 DOCK2 附近的 5q35 (rs60200309-A) 上的一个变异与年轻的严重 COVID-19 (< 65岁）患者（n例=440，优势比=2.01，P =1.2×10 -8）。这种风险等位基因在东亚人中很普遍，但在欧洲人中很少见，显示出非欧洲 GWAS 的价值。473 份大量外周血的 RNA-seq 确定了风险等位基因对年轻患者DOCK2表达的降低影响。码头2在严重形式的 COVID-19 中表达受到抑制。单细胞 RNA-seq 分析 ( n = 61) 确定了 DOCK2 的细胞类型特异性下调和风险等位基因对DOCK2的COVID -19 特异性降低作用在非经典单核细胞中。来自严重 COVID-19 肺炎的肺标本的免疫组织化学显示 DOCK2 受到抑制。此外，使用 CPYPP 抑制 DOCK2 功能会在 SARS-CoV-2 感染的叙利亚仓鼠模型中诱发更严重的肺炎，其特征是体重减轻、肺水肿、病毒载量增加、巨噬细胞募集受损和 I 型干扰素反应失调。我们得出结论，DOCK2 在宿主对 SARS-CoV-2 感染的免疫反应和严重 COVID-19 的发展中发挥重要作用，并且可以作为潜在的生物标志物和/或治疗靶点进一步探索。
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