Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1

Varalee Yodsurang, Yaqi Tang, Yukie Takahashi, Chizu Tanikawa, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Nobuo Fuse, Junichi Sugawara, Atsushi Shimizu, Akimune Fukushima, Asahi Hishida, Norihiro Furusyo, Mariko Naito, Kenji Wakai, Taiki Yamaji, Norie Sawadai, Motoki Iwasaki, Shoichiro Tsugane, Makoto Hirata & 3 others Yoshinori Murakami, Michiaki Kubo, Koichi Matsuda

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) have identified greater than 30 variants associated with ovarian cancer, but most of these variants were investigated in European populations. Here, we integrated GWAS and subsequent functional analyses to identify the genetic variants with potential regulatory effects. We conducted GWAS for ovarian cancer using 681 Japanese cases and 17,492 controls and found that rs137672 on 22q13.1 exhibited a strong association with a P-value of 1.05 × 10 −7 and an odds ratio of 0.573 with a 95% confidence interval of 0.466–0.703. In addition, three previously reported SNPs, i.e., rs10088218, rs9870207 and rs1400482, were validated in the Japanese population (P < 0.05) with the same risk allele as noted in previous studies. Functional studies including regulatory feature analysis and electrophoretic mobility shift assay (EMSA) revealed two regulatory SNPs in 22q13.1, rs2072872 and rs6509, that affect the binding affinity to some nuclear proteins in ovarian cancer cells. The plausible regulatory proteins whose motifs could be affected by the allele changes of these two SNPs were also proposed. Moreover, the protective G allele of rs6509 was associated with a decreased SYNGR1 expression level in normal ovarian tissues. Our findings elucidated the regulatory variants in 22q13.1 that are associated with ovarian cancer risk.

Original languageEnglish
Article numbere0209096
JournalPloS one
Volume13
Issue number12
DOIs
Publication statusPublished - 01-12-2018

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ovarian neoplasms
Genome-Wide Association Study
Ovarian Neoplasms
Genes
Association reactions
Single Nucleotide Polymorphism
Alleles
alleles
Electrophoretic mobility
Amino Acid Motifs
nuclear proteins
regulatory proteins
Electrophoretic Mobility Shift Assay
Nuclear Proteins
odds ratio
Population
confidence interval
Assays
Odds Ratio
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yodsurang, V., Tang, Y., Takahashi, Y., Tanikawa, C., Kamatani, Y., Takahashi, A., ... Matsuda, K. (2018). Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1. PloS one, 13(12), [e0209096]. https://doi.org/10.1371/journal.pone.0209096
Yodsurang, Varalee ; Tang, Yaqi ; Takahashi, Yukie ; Tanikawa, Chizu ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Momozawa, Yukihide ; Fuse, Nobuo ; Sugawara, Junichi ; Shimizu, Atsushi ; Fukushima, Akimune ; Hishida, Asahi ; Furusyo, Norihiro ; Naito, Mariko ; Wakai, Kenji ; Yamaji, Taiki ; Sawadai, Norie ; Iwasaki, Motoki ; Tsugane, Shoichiro ; Hirata, Makoto ; Murakami, Yoshinori ; Kubo, Michiaki ; Matsuda, Koichi. / Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1. In: PloS one. 2018 ; Vol. 13, No. 12.
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Yodsurang, V, Tang, Y, Takahashi, Y, Tanikawa, C, Kamatani, Y, Takahashi, A, Momozawa, Y, Fuse, N, Sugawara, J, Shimizu, A, Fukushima, A, Hishida, A, Furusyo, N, Naito, M, Wakai, K, Yamaji, T, Sawadai, N, Iwasaki, M, Tsugane, S, Hirata, M, Murakami, Y, Kubo, M & Matsuda, K 2018, 'Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1', PloS one, vol. 13, no. 12, e0209096. https://doi.org/10.1371/journal.pone.0209096

Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1. / Yodsurang, Varalee; Tang, Yaqi; Takahashi, Yukie; Tanikawa, Chizu; Kamatani, Yoichiro; Takahashi, Atsushi; Momozawa, Yukihide; Fuse, Nobuo; Sugawara, Junichi; Shimizu, Atsushi; Fukushima, Akimune; Hishida, Asahi; Furusyo, Norihiro; Naito, Mariko; Wakai, Kenji; Yamaji, Taiki; Sawadai, Norie; Iwasaki, Motoki; Tsugane, Shoichiro; Hirata, Makoto; Murakami, Yoshinori; Kubo, Michiaki; Matsuda, Koichi.

In: PloS one, Vol. 13, No. 12, e0209096, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1

AU - Yodsurang, Varalee

AU - Tang, Yaqi

AU - Takahashi, Yukie

AU - Tanikawa, Chizu

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Momozawa, Yukihide

AU - Fuse, Nobuo

AU - Sugawara, Junichi

AU - Shimizu, Atsushi

AU - Fukushima, Akimune

AU - Hishida, Asahi

AU - Furusyo, Norihiro

AU - Naito, Mariko

AU - Wakai, Kenji

AU - Yamaji, Taiki

AU - Sawadai, Norie

AU - Iwasaki, Motoki

AU - Tsugane, Shoichiro

AU - Hirata, Makoto

AU - Murakami, Yoshinori

AU - Kubo, Michiaki

AU - Matsuda, Koichi

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Genome-wide association studies (GWAS) have identified greater than 30 variants associated with ovarian cancer, but most of these variants were investigated in European populations. Here, we integrated GWAS and subsequent functional analyses to identify the genetic variants with potential regulatory effects. We conducted GWAS for ovarian cancer using 681 Japanese cases and 17,492 controls and found that rs137672 on 22q13.1 exhibited a strong association with a P-value of 1.05 × 10 −7 and an odds ratio of 0.573 with a 95% confidence interval of 0.466–0.703. In addition, three previously reported SNPs, i.e., rs10088218, rs9870207 and rs1400482, were validated in the Japanese population (P < 0.05) with the same risk allele as noted in previous studies. Functional studies including regulatory feature analysis and electrophoretic mobility shift assay (EMSA) revealed two regulatory SNPs in 22q13.1, rs2072872 and rs6509, that affect the binding affinity to some nuclear proteins in ovarian cancer cells. The plausible regulatory proteins whose motifs could be affected by the allele changes of these two SNPs were also proposed. Moreover, the protective G allele of rs6509 was associated with a decreased SYNGR1 expression level in normal ovarian tissues. Our findings elucidated the regulatory variants in 22q13.1 that are associated with ovarian cancer risk.

AB - Genome-wide association studies (GWAS) have identified greater than 30 variants associated with ovarian cancer, but most of these variants were investigated in European populations. Here, we integrated GWAS and subsequent functional analyses to identify the genetic variants with potential regulatory effects. We conducted GWAS for ovarian cancer using 681 Japanese cases and 17,492 controls and found that rs137672 on 22q13.1 exhibited a strong association with a P-value of 1.05 × 10 −7 and an odds ratio of 0.573 with a 95% confidence interval of 0.466–0.703. In addition, three previously reported SNPs, i.e., rs10088218, rs9870207 and rs1400482, were validated in the Japanese population (P < 0.05) with the same risk allele as noted in previous studies. Functional studies including regulatory feature analysis and electrophoretic mobility shift assay (EMSA) revealed two regulatory SNPs in 22q13.1, rs2072872 and rs6509, that affect the binding affinity to some nuclear proteins in ovarian cancer cells. The plausible regulatory proteins whose motifs could be affected by the allele changes of these two SNPs were also proposed. Moreover, the protective G allele of rs6509 was associated with a decreased SYNGR1 expression level in normal ovarian tissues. Our findings elucidated the regulatory variants in 22q13.1 that are associated with ovarian cancer risk.

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Yodsurang V, Tang Y, Takahashi Y, Tanikawa C, Kamatani Y, Takahashi A et al. Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1. PloS one. 2018 Dec 1;13(12). e0209096. https://doi.org/10.1371/journal.pone.0209096