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

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.

SUBMITTER: Takata R

PROVIDER: S-EPMC6764957 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Takata Ryo R Takahashi Atsushi A Fujita Masashi M Momozawa Yukihide Y Saunders Edward J EJ Yamada Hiroki H Maejima Kazuhiro K Nakano Kaoru K Nishida Yuichiro Y Hishida Asahi A Matsuo Keitaro K Wakai Kenji K Yamaji Taiki T Sawada Norie N Iwasaki Motoki M Tsugane Shoichiro S Sasaki Makoto M Shimizu Atsushi A Tanno Kozo K Minegishi Naoko N Suzuki Kichiya K Matsuda Koichi K Kubo Michiaki M Inazawa Johji J Egawa Shin S Haiman Christopher A CA Ogawa Osamu O Obara Wataru W Kamatani Yoichiro Y Akamatsu Shusuke S Nakagawa Hidewaki H

Nature communications 20190927 1

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<sup>-16</sup>), rs73862213 (GATA2, P = 5.87 × 10<sup>-23</sup>), rs7791 ...[more]

PMID: 31562322

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Project description:Coronary artery disease (CAD) and cerebral infarction (CI) remain major causes of morbidity and mortality in humans. Recent genome-wide association studies have identified various genetic variants associated with these diseases. However, these studies were commonly conducted in a cross-sectional manner. Therefore, the present research performed longitudinal exome-wide association studies for CAD and CI using data on ~244,000 genotyped variants and the clinical data of 6,026 Japanese individuals who had attended annual health checkups for several years (mean followed-up period, 5±3 years). Following quality controls, the significance [false discovery rate (FDR) of <0.05] of association of the diseases with 24,651 single nucleotide polymorphisms (SNPs) in 5,989 individuals for three inheritance models was tested using the generalized estimating equation model. SNPs that reached statistical significance were further screened against a threshold of approxdf (a scale of small effective sample size) of >30. The longitudinal exome-wide association studies revealed that three SNPs [rs4606855 of ADGRE3 (P=2.5×10-6; FDR=0.031; approxdf=71), rs3746414 of ZFP64 (P=5.9×10-6; FDR=0.048; approxdf=93) and rs7132908 of FAIM2 (P<2.0×10-16; FDR<4.9×10-12; approxdf=65)] were significantly associated with the prevalence of CAD. A different set of three SNPs [rs6580741 of FAM186A (P<2.0×10-16; FDR<4.9×10-12; approxdf=48), rs1324015 of LINC00400 (P<2.0×10-16; FDR<4.9×10-12; approxdf=49) and rs884205 of TNFRSF11A (P<2.0×10-16; FDR<4.9×10-12; approxdf=32)] was significantly associated with CI. The comparison of disease incidence with these SNPs demonstrated that all the minor alleles were associated with decreased susceptibility to CAD or CI. In conclusion, six novel SNPs were identified as susceptibility loci for CAD (rs4606855 of ADGRE3, rs3746414 of ZFP64, and rs7132908 of FAIM2) or CI (rs6580741 of FAM186A, rs1324015 of LINC00400, and rs884205 of TNFRSF11A).

Dataset Information

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

Publications

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

Similar Datasets

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