TY - JOUR
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
N1 - Publisher Copyright:
© 2018 Yodsurang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/12
Y1 - 2018/12
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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U2 - 10.1371/journal.pone.0209096
DO - 10.1371/journal.pone.0209096
M3 - Article
C2 - 30557369
AN - SCOPUS:85058697361
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 12
M1 - e0209096
ER -
