The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

Qingbo S. Wang,Ryuya Edahiro,Ho Namkoong,Takanori Hasegawa,Yuya Shirai,Kyuto Sonehara,Hiromu Tanaka,Ho Lee,Ryunosuke Saiki,Takayoshi Hyugaji,Eigo Shimizu,Kotoe Katayama,Masahiro Kanai,Tatsuhiko Naito,Noah Sasa,Kenichi Yamamoto,Yasuhiro Kato,Takayoshi Morita,Kazuhisa Takahashi,Norihiro Harada,Toshio Naito,Makoto Hiki,Yasushi Matsushita,Haruhi Takagi,Masako Ichikawa,Ai Nakamura,Sonoko Harada,Yuuki Sandhu,Hiroki Kabata,Katsunori Masaki,Hirofumi Kamata,Shinnosuke Ikemura,Shotaro Chubachi,Satoshi Okamori,Hideki Terai,Atsuho Morita,Takanori Asakura,Junichi Sasaki,Hiroshi Morisaki,Yoshifumi Uwamino,Kosaku Nanki,Sho Uchida,Shunsuke Uno,Tomoyasu Nishimura, Takashri Ishiguro,Taisuke Isono,Shun Shibata,Yuma Matsui,Chiaki Hosoda,Kenji Takano,Takashi Nishida,Yoichi Kobayashi,Yotaro Takaku,Noboru Takayanagi,Soichiro Ueda,Ai Tada,Masayoshi Miyawaki, Masaomi Yamamoto,Eriko Yoshida,Reina Hayashi,Tomoki Nagasaka, Sawako Arai,Yutaro Kaneko, Kana Sasaki,Etsuko Tagaya,Masatoshi Kawana,Ken Arimura,Kunihiko Takahashi,Tatsuhiko Anzai,Satoshi Ito, Akifumi Endo, Yuji Uchimura,Yasunari Miyazaki,Takayuki Honda,Tomoya Tateishi,Shuji Tohda,Naoya Ichimura,Kazunari Sonobe, Chihiro Tani Sassa,Jun Nakajima,Yasushi Nakano,Yukiko Nakajima,Ryusuke Anan,Ryosuke Arai,Yuko Kurihara, Yuko Harada,Kazumi Nishio,Tetsuya Ueda, Masanori Azuma,Ryuichi Saito, Toshikatsu Sado,Yoshimune Miyazaki,Ryuichi Sato, Yuki Haruta,Tadao Nagasaki,Yoshinori Yasui,Yoshinori Hasegawa,Yoshikazu Mutoh,Tomoki Kimura,Tomonori Sato,Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi,Yasuhiko Yamano,Hajime Sasano,Sho Ota,Yasushi Nakamori,Kazuhisa Yoshiya,Fukuki Saito,Tomoyuki Yoshihara,Daiki Wada,Hiromu Iwamura, Syuji Kanayama,Shuhei Maruyama,Takashi Yoshiyama, Ken Ohta,Hiroyuki Kokuto,Hideo Ogata,Yoshiaki Tanaka,Kenichi Arakawa,Masafumi Shimoda,Takeshi Osawa,Hiroki Tateno,Isano Hase,Shuichi Yoshida,Shoji Suzuki, Miki Kawada,Hirohisa Horinouchi,Fumitake Saito,Keiko Mitamura,Masao Hagihara,Junichi Ochi, Tomoyuki Uchida,Rie Baba,Daisuke Arai,Takayuki Ogura,Hidenori Takahashi,Shigehiro Hagiwara,Genta Nagao, Shunichiro Konishi,Ichiro Nakachi,Koji Murakami,Mitsuhiro Yamada,Hisatoshi Sugiura,Hirohito Sano,Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono,Hiroaki Baba,Yusuke Suzuki,Sohei Nakayama,Keita Masuzawa,Shinichi Namba,Takayuki Shiroyama,Yoshimi Noda,Takayuki Niitsu,Yuichi Adachi,Takatoshi Enomoto,Saori Amiya,Reina Hara,Yuta Yamaguchi,Teruaki Murakami,Tomoki Kuge, Kinnosuke Matsumoto,Yuji Yamamoto,Makoto Yamamoto,Midori Yoneda, Kazunori Tomono,Kazuto Kato,Haruhiko Hirata,Yoshito Takeda,Hidefumi Koh,Tadashi Manabe,Yohei Funatsu,Fumimaro Ito,Takahiro Fukui,Keisuke Shinozuka,Sumiko Kohashi,Masatoshi Miyazaki, Tomohisa Shoko,Mitsuaki Kojima,Tomohiro Adachi, Motonao Ishikawa,Kenichiro Takahashi,Takashi Inoue,Toshiyuki Hirano,Keigo Kobayashi, Hatsuyo Takaoka,Kazuyoshi Watanabe,Naoki Miyazawa,Yasuhiro Kimura,Reiko Sado, Hideyasu Sugimoto, Akane Kamiya,Naota Kuwahara,Akiko Fujiwara,Tomohiro Matsunaga,Yoko Sato,Takenori Okada, Yoshihiro Hirai,Hidetoshi Kawashima, Atsuya Narita,Kazuki Niwa,Yoshiyuki Sekikawa,Koichi Nishi,Masaru Nishitsuji, Mayuko Tani,Junya Suzuki, Hiroki Nakatsumi,Takashi Ogura,Hideya Kitamura,Eri Hagiwara,Kota Murohashi,Hiroko Okabayashi,Takao Mochimaru,Shigenari Nukaga,Ryosuke Satomi,Yoshitaka Oyamada,Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo,Yasushi Makino,Kazuma Yagi,Mizuha Hashiguchi,Junko Kagyo,Tetsuya Shiomi, Satoshi Fuke,Hiroshi Saito, Tomoya Tsuchida,Shigeki Fujitani, Mumon Takita, Daiki Morikawa,Toru Yoshida,Takehiro Izumo,Minoru Inomata,Naoyuki Kuse,Nobuyasu Awano,Mari Tone,Akihiro Ito,Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama,Hiroyasu Ishikura,Tohru Takata,Toshio Odani,Masaru Amishima,Takeshi Hattori,Yasuo Shichinohe, Takashi Kagaya,Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami,Kiyoshi Koshida,Kentaro Hayashi,Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma,Yasuhiro Gon,Namiki Izumi,Kaoru Nagata,Ken Ueda,Reiko Taki,Satoko Hanada,Kodai Kawamura,Kazuya Ichikado,Kenta Nishiyama, Hiroyuki Muranaka,Kazunori Nakamura,Naozumi Hashimoto,Keiko Wakahara,Sakamoto Koji,Norihito Omote,Akira Ando,Nobuhiro Kodama, Yasunari Kaneyama,Shunsuke Maeda, Takashige Kuraki,Takemasa Matsumoto,Koutaro Yokote,Taka-Aki Nakada,Ryuzo Abe,Taku Oshima,Tadanaga Shimada,Masahiro Harada, Takeshi Takahashi,Hiroshi Ono,Toshihiro Sakurai, Takayuki Shibusawa,Yoshifumi Kimizuka,Akihiko Kawana,Tomoya Sano,Chie Watanabe, Ryohei Suematsu, Hisako Sageshima,Ayumi Yoshifuji,Kazuto Ito,Saeko Takahashi,Kota Ishioka,Morio Nakamura, Makoto Masuda, Aya Wakabayashi,Hiroki Watanabe, Suguru Ueda,Masanori Nishikawa,Yusuke Chihara,Mayumi Takeuchi, Keisuke Onoi,Jun Shinozuka,Atsushi Sueyoshi,Yoji Nagasaki,Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo,Yoshihisa Tokunaga, Yu Kusaka,Takehiko Ohba, Susumu Isogai, Aki Ogawa,Takuya Inoue, Satoru Fukuyama,Yoshihiro Eriguchi, Akiko Yonekawa,Keiko Kan-o, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara,Kiyoshi Komuta,Yoshiaki Inoue,Shigeru Chiba,Kunihiro Yamagata,Yuji Hiramatsu,Hirayasu Kai,Koichiro Asano,Tsuyoshi Oguma,Yoko Ito,Satoru Hashimoto, Masaki Yamasaki,Yu Kasamatsu,Yuko Komase,Naoya Hida,Takahiro Tsuburai, Baku Oyama,Minoru Takada,Hidenori Kanda, Yuichiro Kitagawa,Tetsuya Fukuta,Takahito Miyake,Shozo Yoshida,Shinji Ogura,Shinji Abe, Yuta Kono,Yuki Togashi, Hiroyuki Takoi,Ryota Kikuchi, Shinichi Ogawa,Tomouki Ogata,Shoichiro Ishihara, Arihiko Kanehiro,Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto,Kei Nishiyama, Mariko Terashima,Satoru Beppu,Kosuke Yoshida,Osamu Narumoto,Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi,Akira Umeda,Kazuya Miyagawa,Hisato Shimada, Mayu Endo,Yoshiyuki Ohira,Masafumi Watanabe,Sumito Inoue,Akira Igarashi,Masamichi Sato,Hironori Sagara,Akihiko Tanaka,Shin Ohta,Tomoyuki Kimura,Yoko Shibata,Yoshinori Tanino, Takefumi Nikaido,Hiroyuki Minemura,Yuki Sato,Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe,Hiroshi Takahashi,Kazuhiko Fujii,Hiroto Kishi,Masayuki Kanai, Tomonori Imamura,Tatsuya Yamashita,Masakiyo Yatomi,Toshitaka Maeno,Shinichi Hayashi,Mai Takahashi,Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga,Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono,Toru Tanaka, Takeru Kashiwada, Kazue Fujita,Yoshinobu Saito,Masahiro Seike,Hiroko Watanabe,Hiroto Matsuse,Norio Kodaka, Chihiro Nakano, Takeshi Oshio,Takatomo Hirouchi, Shohei Makino,Moritoki Egi,Yosuke Omae,Yasuhito Nannya,Takafumi Ueno,Tomomi Takano,Kazuhiko Katayama,Masumi Ai,Atsushi Kumanogoh,Toshiro Sato,Naoki Hasegawa,Katsushi Tokunaga,Makoto Ishii,Ryuji Koike,Yuko Kitagawa,Akinori Kimura,Seiya Imoto,Satoru Miyano,Seishi Ogawa,Takanori Kanai,Koichi Fukunaga,Yukinori Okada

NATURE COMMUNICATIONS(2022)

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摘要
Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1 ), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1 ), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2 ). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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Gene expression,Quantitative trait loci,Transcriptomics,Viral infection,Science,Humanities and Social Sciences,multidisciplinary
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