Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer

Yingsong Lin; Masahiro Nakatochi; Yasuyuki Hosono; Hidemi Ito; Yoichiro Kamatani; Akihito Inoko; Hiromi Sakamoto; Fumie Kinoshita; Yumiko Kobayashi; Hiroshi Ishii; Masato Ozaka; Takashi Sasaki; Masato Matsuyama; Naoki Sasahira; Manabu Morimoto; Satoshi Kobayashi; Taito Fukushima; Makoto Ueno; Shinichi Ohkawa; Naoto Egawa; Sawako Kuruma; Mitsuru Mori; Haruhisa Nakao; Yasushi Adachi; Masumi Okuda; Takako Osaki; Shigeru Kamiya; Chaochen Wang; Kazuo Hara; Yasuhiro Shimizu; Tatsuo Miyamoto; Yuko Hayashi; Hiromichi Ebi; Tomohiro Kohmoto; Issei Imoto; Yumiko Kasugai; Yoshinori Murakami; Masato Akiyama; Kazuyoshi Ishigaki; Koichi Matsuda; Makoto Hirata; Kazuaki Shimada; Takuji Okusaka; Takahisa Kawaguchi; Meiko Takahashi; Yoshiyuki Watanabe; Kiyonori Kuriki; Aya Kadota; Rieko Okada; Haruo Mikami; Toshiro Takezaki; Sadao Suzuki; Taiki Yamaji; Motoki Iwasaki; Norie Sawada; Atsushi Goto; Kengo Kinoshita; Nobuo Fuse; Fumiki Katsuoka; Atsushi Shimizu; Satoshi S. Nishizuka; Kozo Tanno; Ken Suzuki; Yukinori Okada; Momoko Horikoshi; Toshimasa Yamauchi; Takashi Kadowaki; Herbert Yu; Jun Zhong; Laufey T. Amundadottir; Yuichiro Doki; Hideshi Ishii; Hidetoshi Eguchi; David Bogumil; Christopher A. Haiman; Loic Le Marchand; Masaki Mori; Harvey Risch; Veronica W. Setiawan; Shoichiro Tsugane; Kenji Wakai; Teruhiko Yoshida; Fumihiko Matsuda; Michiaki Kubo; Shogo Kikuchi; Keitaro Matsuo

doi:10.1038/s41467-020-16711-w

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer

Yingsong Lin, Masahiro Nakatochi, Yasuyuki Hosono, Hidemi Ito, Yoichiro Kamatani, Akihito Inoko, Hiromi Sakamoto, Fumie Kinoshita, Yumiko Kobayashi, Hiroshi Ishii, Masato Ozaka, Takashi Sasaki, Masato Matsuyama, Naoki Sasahira, Manabu Morimoto, Satoshi Kobayashi, Taito Fukushima, Makoto Ueno, Shinichi Ohkawa, Naoto EgawaSawako Kuruma, Mitsuru Mori, Haruhisa Nakao, Yasushi Adachi, Masumi Okuda, Takako Osaki, Shigeru Kamiya, Chaochen Wang, Kazuo Hara, Yasuhiro Shimizu, Tatsuo Miyamoto, Yuko Hayashi, Hiromichi Ebi, Tomohiro Kohmoto, Issei Imoto, Yumiko Kasugai, Yoshinori Murakami, Masato Akiyama, Kazuyoshi Ishigaki, Koichi Matsuda, Makoto Hirata, Kazuaki Shimada, Takuji Okusaka, Takahisa Kawaguchi, Meiko Takahashi, Yoshiyuki Watanabe, Kiyonori Kuriki, Aya Kadota, Rieko Okada, Haruo Mikami, Toshiro Takezaki, Sadao Suzuki, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Atsushi Goto, Kengo Kinoshita, Nobuo Fuse, Fumiki Katsuoka, Atsushi Shimizu, Satoshi S. Nishizuka, Kozo Tanno, Ken Suzuki, Yukinori Okada, Momoko Horikoshi, Toshimasa Yamauchi, Takashi Kadowaki, Herbert Yu, Jun Zhong, Laufey T. Amundadottir, Yuichiro Doki, Hideshi Ishii, Hidetoshi Eguchi, David Bogumil, Christopher A. Haiman, Loic Le Marchand, Masaki Mori, Harvey Risch, Veronica W. Setiawan, Shoichiro Tsugane, Kenji Wakai, Teruhiko Yoshida, Fumihiko Matsuda, Michiaki Kubo, Shogo Kikuchi, Keitaro Matsuo

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Abstract

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10⁻⁸), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10⁻⁹), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Original language	English
Article number	3175
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16711-w
State	Published - 1 Dec 2020
Externally published	Yes

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Lin, Y., Nakatochi, M., Hosono, Y., Ito, H., Kamatani, Y., Inoko, A., Sakamoto, H., Kinoshita, F., Kobayashi, Y., Ishii, H., Ozaka, M., Sasaki, T., Matsuyama, M., Sasahira, N., Morimoto, M., Kobayashi, S., Fukushima, T., Ueno, M., Ohkawa, S., ... Matsuo, K. (2020). Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer. Nature Communications, 11(1), Article 3175. https://doi.org/10.1038/s41467-020-16711-w

@article{eafef60cea784c90a47d9ceca8b0f2fa,

title = "Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer",

abstract = "Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10−8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10−9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.",

author = "Yingsong Lin and Masahiro Nakatochi and Yasuyuki Hosono and Hidemi Ito and Yoichiro Kamatani and Akihito Inoko and Hiromi Sakamoto and Fumie Kinoshita and Yumiko Kobayashi and Hiroshi Ishii and Masato Ozaka and Takashi Sasaki and Masato Matsuyama and Naoki Sasahira and Manabu Morimoto and Satoshi Kobayashi and Taito Fukushima and Makoto Ueno and Shinichi Ohkawa and Naoto Egawa and Sawako Kuruma and Mitsuru Mori and Haruhisa Nakao and Yasushi Adachi and Masumi Okuda and Takako Osaki and Shigeru Kamiya and Chaochen Wang and Kazuo Hara and Yasuhiro Shimizu and Tatsuo Miyamoto and Yuko Hayashi and Hiromichi Ebi and Tomohiro Kohmoto and Issei Imoto and Yumiko Kasugai and Yoshinori Murakami and Masato Akiyama and Kazuyoshi Ishigaki and Koichi Matsuda and Makoto Hirata and Kazuaki Shimada and Takuji Okusaka and Takahisa Kawaguchi and Meiko Takahashi and Yoshiyuki Watanabe and Kiyonori Kuriki and Aya Kadota and Rieko Okada and Haruo Mikami and Toshiro Takezaki and Sadao Suzuki and Taiki Yamaji and Motoki Iwasaki and Norie Sawada and Atsushi Goto and Kengo Kinoshita and Nobuo Fuse and Fumiki Katsuoka and Atsushi Shimizu and Nishizuka, {Satoshi S.} and Kozo Tanno and Ken Suzuki and Yukinori Okada and Momoko Horikoshi and Toshimasa Yamauchi and Takashi Kadowaki and Herbert Yu and Jun Zhong and Amundadottir, {Laufey T.} and Yuichiro Doki and Hideshi Ishii and Hidetoshi Eguchi and David Bogumil and Haiman, {Christopher A.} and {Le Marchand}, Loic and Masaki Mori and Harvey Risch and Setiawan, {Veronica W.} and Shoichiro Tsugane and Kenji Wakai and Teruhiko Yoshida and Fumihiko Matsuda and Michiaki Kubo and Shogo Kikuchi and Keitaro Matsuo",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-16711-w",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

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Lin, Y, Nakatochi, M, Hosono, Y, Ito, H, Kamatani, Y, Inoko, A, Sakamoto, H, Kinoshita, F, Kobayashi, Y, Ishii, H, Ozaka, M, Sasaki, T, Matsuyama, M, Sasahira, N, Morimoto, M, Kobayashi, S, Fukushima, T, Ueno, M, Ohkawa, S, Egawa, N, Kuruma, S, Mori, M, Nakao, H, Adachi, Y, Okuda, M, Osaki, T, Kamiya, S, Wang, C, Hara, K, Shimizu, Y, Miyamoto, T, Hayashi, Y, Ebi, H, Kohmoto, T, Imoto, I, Kasugai, Y, Murakami, Y, Akiyama, M, Ishigaki, K, Matsuda, K, Hirata, M, Shimada, K, Okusaka, T, Kawaguchi, T, Takahashi, M, Watanabe, Y, Kuriki, K, Kadota, A, Okada, R, Mikami, H, Takezaki, T, Suzuki, S, Yamaji, T, Iwasaki, M, Sawada, N, Goto, A, Kinoshita, K, Fuse, N, Katsuoka, F, Shimizu, A, Nishizuka, SS, Tanno, K, Suzuki, K, Okada, Y, Horikoshi, M, Yamauchi, T, Kadowaki, T, Yu, H, Zhong, J, Amundadottir, LT, Doki, Y, Ishii, H, Eguchi, H, Bogumil, D, Haiman, CA, Le Marchand, L, Mori, M, Risch, H, Setiawan, VW, Tsugane, S, Wakai, K, Yoshida, T, Matsuda, F, Kubo, M, Kikuchi, S & Matsuo, K 2020, 'Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer', Nature Communications, vol. 11, no. 1, 3175. https://doi.org/10.1038/s41467-020-16711-w

TY - JOUR

T1 - Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer

AU - Lin, Yingsong

AU - Nakatochi, Masahiro

AU - Hosono, Yasuyuki

AU - Ito, Hidemi

AU - Kamatani, Yoichiro

AU - Inoko, Akihito

AU - Sakamoto, Hiromi

AU - Kinoshita, Fumie

AU - Kobayashi, Yumiko

AU - Ishii, Hiroshi

AU - Ozaka, Masato

AU - Sasaki, Takashi

AU - Matsuyama, Masato

AU - Sasahira, Naoki

AU - Morimoto, Manabu

AU - Kobayashi, Satoshi

AU - Fukushima, Taito

AU - Ueno, Makoto

AU - Ohkawa, Shinichi

AU - Egawa, Naoto

AU - Kuruma, Sawako

AU - Mori, Mitsuru

AU - Nakao, Haruhisa

AU - Adachi, Yasushi

AU - Okuda, Masumi

AU - Osaki, Takako

AU - Kamiya, Shigeru

AU - Wang, Chaochen

AU - Hara, Kazuo

AU - Shimizu, Yasuhiro

AU - Miyamoto, Tatsuo

AU - Hayashi, Yuko

AU - Ebi, Hiromichi

AU - Kohmoto, Tomohiro

AU - Imoto, Issei

AU - Kasugai, Yumiko

AU - Murakami, Yoshinori

AU - Akiyama, Masato

AU - Ishigaki, Kazuyoshi

AU - Matsuda, Koichi

AU - Hirata, Makoto

AU - Shimada, Kazuaki

AU - Okusaka, Takuji

AU - Kawaguchi, Takahisa

AU - Takahashi, Meiko

AU - Watanabe, Yoshiyuki

AU - Kuriki, Kiyonori

AU - Kadota, Aya

AU - Okada, Rieko

AU - Mikami, Haruo

AU - Takezaki, Toshiro

AU - Suzuki, Sadao

AU - Yamaji, Taiki

AU - Iwasaki, Motoki

AU - Sawada, Norie

AU - Goto, Atsushi

AU - Kinoshita, Kengo

AU - Fuse, Nobuo

AU - Katsuoka, Fumiki

AU - Shimizu, Atsushi

AU - Nishizuka, Satoshi S.

AU - Tanno, Kozo

AU - Suzuki, Ken

AU - Okada, Yukinori

AU - Horikoshi, Momoko

AU - Yamauchi, Toshimasa

AU - Kadowaki, Takashi

AU - Yu, Herbert

AU - Zhong, Jun

AU - Amundadottir, Laufey T.

AU - Doki, Yuichiro

AU - Ishii, Hideshi

AU - Eguchi, Hidetoshi

AU - Bogumil, David

AU - Haiman, Christopher A.

AU - Le Marchand, Loic

AU - Mori, Masaki

AU - Risch, Harvey

AU - Setiawan, Veronica W.

AU - Tsugane, Shoichiro

AU - Wakai, Kenji

AU - Yoshida, Teruhiko

AU - Matsuda, Fumihiko

AU - Kubo, Michiaki

AU - Kikuchi, Shogo

AU - Matsuo, Keitaro

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10−8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10−9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

AB - Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10−8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10−9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

UR - http://www.scopus.com/inward/record.url?scp=85086824587&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-16711-w

DO - 10.1038/s41467-020-16711-w

M3 - Article

C2 - 32581250

AN - SCOPUS:85086824587

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3175

ER -

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer

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