Genome-wide association meta-analysis identifies novel GP2 gene risk variants for pancreatic cancer in the Japanese population
By
Yingsong Lin,
Masahiro Nakatochi,
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,
Yasuyuki Hosono,
Hiromichi Ebi,
Tomohiro Kohmoto,
Issei Imoto,
Yoshinori Murakami,
Masato Akiyama,
Kazuyoshi Ishigaki,
Koichi Matsuda,
Makoto Hirata,
Katsuaki Shimada,
Takuji Okusaka,
Takahisa Kawaguchi,
Meiko Takahashi,
Yoshiyuki Watanabe,
Kiyonori Kuriki,
Aya Kadota,
Kenji Wakai,
Taiki Yamaji,
Motoki Iwasaki,
Norie Sawada,
Shoichiro Tsugane,
Kengo Kinoshita,
Nobuo Fuse,
Fumiki Katsuoka,
Atsushi Shimizu,
Satoshi S. Nishizuka,
Kozo Tanno,
Ken Suzuki,
Yukinori Okada,
Momoko Horikoshi,
Toshimasa Yamauchi,
Takashi Kadowaki,
Teruhiko Yoshida,
Fumihiko Matsuda,
Michiaki Kubo,
Shogo Kikuchi,
Keitaro Matsuo
Posted 19 Dec 2018
bioRxiv DOI: 10.1101/498659
The etiology of pancreatic cancer remains largely unknown. Here, we report the results of a meta-analysis of three genome-wide association studies (GWASs) comprising 2,039 pancreatic cancer cases and 32,592 controls, the largest sample size in the Japanese population. We identified 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P<5.0×10-8) and 4 suggestive loci (P<1.0×10-6) for pancreatic cancer. Of these risk loci, 16p12.3 is novel; the lead SNP maps to rs78193826 (odds ratio (OR)=1.46, 95% CI=1.29-1.66, P=4.28×10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant predicted to be highly deleterious. Additionally, the gene-based GWAS identified a novel gene, KRT8, which is linked to exocrine pancreatic and liver diseases. The identified GP2 gene variants were pleiotropic for multiple traits, including type 2 diabetes, hemoglobin A1c (HbA1c) levels, and pancreatic cancer. Mendelian randomization analyses corroborated causality between HbA1c and pancreatic cancer. These findings suggest that GP2 gene variants are associated with pancreatic cancer susceptibility in the Japanese population, prompting further functional characterization of this locus.
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