Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals

Masao Nagasaki; Jun Yasuda; Fumiki Katsuoka; Naoki Nariai; Kaname Kojima; Yosuke Kawai; Yumi Yamaguchi-Kabata; Junji Yokozawa; Inaho Danjoh; Sakae Saito; Yukuto Sato; Takahiro Mimori; Kaoru Tsuda; Rumiko Saito; Xiaoqing Pan; Satoshi Nishikawa; Shin Ito; Yoko Kuroki; Osamu Tanabe; Nobuo Fuse; Shinichi Kuriyama; Hideyasu Kiyomoto; Atsushi Hozawa; Naoko Minegishi; James Douglas Engel; Kengo Kinoshita; Shigeo Kure; Nobuo Yaegashi; Masayuki Yamamoto; Akito Tsuboi; Fuji Nagami; Hiroshi Kawame; Hiroaki Tomita; Ichiro Tsuji; Jun Nakaya; Junichi Sugawara; Kichiya Suzuki; Masahiro Kikuya; Michiaki Abe; Naoki Nakaya; Noriko Osumi; Riu Yamashita; Soichi Ogishima; Takako Takai; Teiji Tominaga; Yasuyuki Taki; Yoichi Suzuki

doi:10.1038/ncomms9018

Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals

Masao Nagasaki^*, Jun Yasuda, Fumiki Katsuoka, Naoki Nariai, Kaname Kojima, Yosuke Kawai, Yumi Yamaguchi-Kabata, Junji Yokozawa, Inaho Danjoh, Sakae Saito, Yukuto Sato, Takahiro Mimori, Kaoru Tsuda, Rumiko Saito, Xiaoqing Pan, Satoshi Nishikawa, Shin Ito, Yoko Kuroki, Osamu Tanabe, Nobuo FuseShinichi Kuriyama, Hideyasu Kiyomoto, Atsushi Hozawa, Naoko Minegishi, James Douglas Engel, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto, Akito Tsuboi, Fuji Nagami, Hiroshi Kawame, Hiroaki Tomita, Ichiro Tsuji, Jun Nakaya, Junichi Sugawara, Kichiya Suzuki, Masahiro Kikuya, Michiaki Abe, Naoki Nakaya, Noriko Osumi, Riu Yamashita, Soichi Ogishima, Takako Takai, Teiji Tominaga, Yasuyuki Taki, Yoichi Suzuki

^*Corresponding author for this work

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

271 Citations (Scopus)

Abstract

The Tohoku Medical Megabank Organization reports the whole-genome sequences of 1,070 healthy Japanese individuals and construction of a Japanese population reference panel (1KJPN). Here we identify through this high-coverage sequencing (32.4 × on average), 21.2 million, including 12 million novel, single-nucleotide variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed analysis detected signatures for purifying selection on regulatory elements as well as coding regions. We also catalogue structural variants, including 3.4 million insertions and deletions, and 25,923 genic copy-number variants. The 1KJPN was effective for imputing genotypes of the Japanese population genome wide. These data demonstrate the value of high-coverage sequencing for constructing population-specific variant panels, which covers 99.0% SNVs of minor allele frequency ≥0.1%, and its value for identifying causal rare variants of complex human disease phenotypes in genetic association studies.

Original language	English
Article number	8018
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9018
Publication status	Published - 2015 Aug 21
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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Nagasaki, M., Yasuda, J., Katsuoka, F., Nariai, N., Kojima, K., Kawai, Y., Yamaguchi-Kabata, Y., Yokozawa, J., Danjoh, I., Saito, S., Sato, Y., Mimori, T., Tsuda, K., Saito, R., Pan, X., Nishikawa, S., Ito, S., Kuroki, Y., Tanabe, O., ... Suzuki, Y. (2015). Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nature communications, 6, [8018]. https://doi.org/10.1038/ncomms9018

Nagasaki, M, Yasuda, J, Katsuoka, F, Nariai, N, Kojima, K, Kawai, Y, Yamaguchi-Kabata, Y, Yokozawa, J, Danjoh, I, Saito, S, Sato, Y, Mimori, T, Tsuda, K, Saito, R, Pan, X, Nishikawa, S, Ito, S, Kuroki, Y, Tanabe, O, Fuse, N, Kuriyama, S, Kiyomoto, H, Hozawa, A, Minegishi, N, Engel, JD, Kinoshita, K, Kure, S, Yaegashi, N, Yamamoto, M, Tsuboi, A, Nagami, F, Kawame, H, Tomita, H, Tsuji, I, Nakaya, J, Sugawara, J, Suzuki, K, Kikuya, M, Abe, M, Nakaya, N, Osumi, N, Yamashita, R, Ogishima, S, Takai, T, Tominaga, T, Taki, Y & Suzuki, Y 2015, 'Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals', Nature communications, vol. 6, 8018. https://doi.org/10.1038/ncomms9018

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title = "Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals",

abstract = "The Tohoku Medical Megabank Organization reports the whole-genome sequences of 1,070 healthy Japanese individuals and construction of a Japanese population reference panel (1KJPN). Here we identify through this high-coverage sequencing (32.4 × on average), 21.2 million, including 12 million novel, single-nucleotide variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed analysis detected signatures for purifying selection on regulatory elements as well as coding regions. We also catalogue structural variants, including 3.4 million insertions and deletions, and 25,923 genic copy-number variants. The 1KJPN was effective for imputing genotypes of the Japanese population genome wide. These data demonstrate the value of high-coverage sequencing for constructing population-specific variant panels, which covers 99.0% SNVs of minor allele frequency ≥0.1%, and its value for identifying causal rare variants of complex human disease phenotypes in genetic association studies.",

author = "Masao Nagasaki and Jun Yasuda and Fumiki Katsuoka and Naoki Nariai and Kaname Kojima and Yosuke Kawai and Yumi Yamaguchi-Kabata and Junji Yokozawa and Inaho Danjoh and Sakae Saito and Yukuto Sato and Takahiro Mimori and Kaoru Tsuda and Rumiko Saito and Xiaoqing Pan and Satoshi Nishikawa and Shin Ito and Yoko Kuroki and Osamu Tanabe and Nobuo Fuse and Shinichi Kuriyama and Hideyasu Kiyomoto and Atsushi Hozawa and Naoko Minegishi and Engel, {James Douglas} and Kengo Kinoshita and Shigeo Kure and Nobuo Yaegashi and Masayuki Yamamoto and Akito Tsuboi and Fuji Nagami and Hiroshi Kawame and Hiroaki Tomita and Ichiro Tsuji and Jun Nakaya and Junichi Sugawara and Kichiya Suzuki and Masahiro Kikuya and Michiaki Abe and Naoki Nakaya and Noriko Osumi and Riu Yamashita and Soichi Ogishima and Takako Takai and Teiji Tominaga and Yasuyuki Taki and Yoichi Suzuki",

note = "Funding Information: This work was supported (in part) by the Tohoku Medical Megabank Project (Special Account for reconstruction from the Great East Japan Earthquake). All computational resources were provided by the ToMMo supercomputer system (http://sc.megabank.to-hoku.ac.jp/en). We are indebted to all volunteers who participated in this ToMMo project. We thank members of ToMMo at the Tohoku University for seminal contribution to the establishment of the genome cohort and biobank and for help in the genome analyses. The member list of ToMMo at the Tohoku University is available in the following website http://www.megabank.tohoku.ac.jp/english/a141201. We thank the members of Iwate ToMMo at the Iwate Medical University, especially Drs Kenji Sobue, Jiro Hitomi and Atsushi Shimizu, for discussion. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

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doi = "10.1038/ncomms9018",

language = "English",

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AU - Nagasaki, Masao

AU - Yasuda, Jun

AU - Katsuoka, Fumiki

AU - Nariai, Naoki

AU - Kojima, Kaname

AU - Kawai, Yosuke

AU - Yamaguchi-Kabata, Yumi

AU - Yokozawa, Junji

AU - Danjoh, Inaho

AU - Saito, Sakae

AU - Sato, Yukuto

AU - Mimori, Takahiro

AU - Tsuda, Kaoru

AU - Saito, Rumiko

AU - Pan, Xiaoqing

AU - Nishikawa, Satoshi

AU - Ito, Shin

AU - Kuroki, Yoko

AU - Tanabe, Osamu

AU - Fuse, Nobuo

AU - Kuriyama, Shinichi

AU - Kiyomoto, Hideyasu

AU - Hozawa, Atsushi

AU - Minegishi, Naoko

AU - Engel, James Douglas

AU - Kinoshita, Kengo

AU - Kure, Shigeo

AU - Yaegashi, Nobuo

AU - Yamamoto, Masayuki

AU - Tsuboi, Akito

AU - Nagami, Fuji

AU - Kawame, Hiroshi

AU - Tomita, Hiroaki

AU - Tsuji, Ichiro

AU - Nakaya, Jun

AU - Sugawara, Junichi

AU - Suzuki, Kichiya

AU - Kikuya, Masahiro

AU - Abe, Michiaki

AU - Nakaya, Naoki

AU - Osumi, Noriko

AU - Yamashita, Riu

AU - Ogishima, Soichi

AU - Takai, Takako

AU - Tominaga, Teiji

AU - Taki, Yasuyuki

AU - Suzuki, Yoichi

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PY - 2015/8/21

Y1 - 2015/8/21

N2 - The Tohoku Medical Megabank Organization reports the whole-genome sequences of 1,070 healthy Japanese individuals and construction of a Japanese population reference panel (1KJPN). Here we identify through this high-coverage sequencing (32.4 × on average), 21.2 million, including 12 million novel, single-nucleotide variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed analysis detected signatures for purifying selection on regulatory elements as well as coding regions. We also catalogue structural variants, including 3.4 million insertions and deletions, and 25,923 genic copy-number variants. The 1KJPN was effective for imputing genotypes of the Japanese population genome wide. These data demonstrate the value of high-coverage sequencing for constructing population-specific variant panels, which covers 99.0% SNVs of minor allele frequency ≥0.1%, and its value for identifying causal rare variants of complex human disease phenotypes in genetic association studies.

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Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals

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