title: Exome-based genome-wide association study and risk assessment using genetic risk score to prostate cancer in the Korean population.
abstract: OBJECTIVE
  To investigate exome-wide genetic variants associated with prostate cancer (PCa) in Koreans and evaluate the discriminative ability by the genetic risk score (GRS).
  
  
  METHODS
  We prospectively recruited 1,001 PCa cases from a tertiary hospital and conducted a case-control study including 2,641 healthy men (Stage I). Participants were analyzed using HumanExome BeadChip. For the external validation, additionally enrolled 514 PCa cases and 548 controls (independent cohort) were analyzed for the identified single nucleotide polymorphisms (SNPs) of Stage I (Stage II). The GRS was calculated as a non-weighted sum of the risk allele counts and investigated for accuracy of prediction of PCa.
  
  
  RESULTS
  the mean age was 66.3 years, and the median level of prostate specific antigen (PSA) was 9.19 ng/ml in PCa cases. In Stage I, 4 loci containing 5 variants (rs1512268 on 8p21.2; rs1016343 and rs7837688 on 8q24.21; rs7501939 on 17q12, and rs2735839 on 19q13.33) were confirmed to reach exome-wide significance (p<8.3x10-7). In Stage II, the mean GRS was 4.23 ± 1.44 for the controls and 4.78 ± 1.43 for the cases. As a reference to GRS 4, GRS 6, 7 and 8 showed a statistically significant risk of PCa (OR=1.85, 2.11 and 3.34, respectively).
  
  
  CONCLUSIONS
  The five variants were validated to associate with PCa in firstly performed exome-wide study in Koreans. The addition of individualized calculated GRS effectively enhanced the accuracy of prediction. These results need to be validated in future studies.
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Oh
authors.affiliation: Complex Disease and Genome Epidemiology Branch, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: Soo Ji
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Structural & Functional genomics, Center for Genome Science, Korean National Institute of Health, KCDC, Korea.
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA.
authors.forename: Dokyoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Hong
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jin-Nyoung
authors.initials: JN
authors.lastname: Ho
authors.affiliation: Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea.
authors.forename: Sungroh
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Complex Disease and Genome Epidemiology Branch, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: Joohon
authors.initials: J
authors.lastname: Sung
authors.affiliation: Department of Urology, Chung Buk National University Hospital, Cheongju, Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Urology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Seok-Soo
authors.initials: SS
authors.lastname: Byun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D059472:Exome; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment
keywords: Korean; exome; prostate; prostate cancer