12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population

Ryo Takata, Atsushi Takahashi, Masashi Fujita, Yukihide Momozawa, Edward J. Saunders, Hiroki Yamada, Kazuhiro Maejima, Kaoru Nakano, Yuichiro Nishida, Asahi Hishida, Keitaro Matsuo, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Makoto Sasaki, Atsushi Shimizu, Kozo Tanno, Naoko MinegishiKichiya Suzuki, Koichi Matsuda, Michiaki Kubo, Johji Inazawa, Shin Egawa, Christopher A. Haiman, Osamu Ogawa, Wataru Obara, Yoichiro Kamatani, Shusuke Akamatsu, Hidewaki Nakagawa

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2 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) have identified ~170 genetic loci associated with prostate cancer (PCa) risk, but most of them were identified in European populations. We here performed a GWAS and replication study using a large Japanese cohort (9,906 cases and 83,943 male controls) to identify novel susceptibility loci associated with PCa risk. We found 12 novel loci for PCa including rs1125927 (TMEM17, P = 3.95 × 10−16), rs73862213 (GATA2, P = 5.87 × 10−23), rs77911174 (ZMIZ1, P = 5.28 × 10−20), and rs138708 (SUN2, P = 1.13 × 10−15), seven of which had crucially low minor allele frequency in European population. Furthermore, we stratified the polygenic risk for Japanese PCa patients by using 82 SNPs, which were significantly associated with Japanese PCa risk in our study, and found that early onset cases and cases with family history of PCa were enriched in the genetically high-risk population. Our study provides important insight into genetic mechanisms of PCa and facilitates PCa risk stratification in Japanese population.

Original languageEnglish
Article number4422
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

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

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    Takata, R., Takahashi, A., Fujita, M., Momozawa, Y., Saunders, E. J., Yamada, H., Maejima, K., Nakano, K., Nishida, Y., Hishida, A., Matsuo, K., Wakai, K., Yamaji, T., Sawada, N., Iwasaki, M., Tsugane, S., Sasaki, M., Shimizu, A., Tanno, K., ... Nakagawa, H. (2019). 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population. Nature communications, 10(1), [4422]. https://doi.org/10.1038/s41467-019-12267-6