Dataset Information

Population-standardized genetic risk score: the SNP-based method of choice for inherited risk assessment of prostate cancer.

ABSTRACT: Several different approaches are available to clinicians for determining prostate cancer (PCa) risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms (SNPs) has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment. Participants were men (n = 1654) enrolled in a prospective study of PCa development. Genotypes of 59 PCa risk-associated SNPs were available in this cohort. Three methods of calculating SNP-based genetic risk scores (GRSs) were used for the evaluation of individual disease risk such as risk allele count (GRS-RAC), weighted risk allele count (GRS-wRAC), and population-standardized genetic risk score (GRS-PS). Mean GRSs were calculated, and performances were compared using area under the receiver operating characteristic curve (AUC) and positive predictive value (PPV). All SNP-based methods were found to be independently associated with PCa (all P < 0.05; hence their clinical validity). The mean GRSs in men with or without PCa using GRS-RAC were 55.15 and 53.46, respectively, using GRS-wRAC were 7.42 and 6.97, respectively, and using GRS-PS were 1.12 and 0.84, respectively (all P < 0.05 for differences between patients with or without PCa). All three SNP-based methods performed similarly in discriminating PCa from non-PCa based on AUC and in predicting PCa risk based on PPV (all P > 0.05 for comparisons between the three methods), and all three SNP-based methods had a significantly higher AUC than family history (all P < 0.05). Results from this study suggest that while the three most commonly used SNP-based methods performed similarly in discriminating PCa from non-PCa at the population level, GRS-PS is the method of choice for risk assessment at the individual level because its value (where 1.0 represents average population risk) can be easily interpreted regardless of the number of risk-associated SNPs used in the calculation.

SUBMITTER: Conran CA

PROVIDER: S-EPMC4955173 | biostudies-literature | 2016 Jul-Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Population-standardized genetic risk score: the SNP-based method of choice for inherited risk assessment of prostate cancer.

Conran Carly A CA Na Rong R Chen Haitao H Jiang Deke D Lin Xiaoling X Zheng S Lilly SL Brendler Charles B CB Xu Jianfeng J

Asian journal of andrology 20160701 4

Several different approaches are available to clinicians for determining prostate cancer (PCa) risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms (SNPs) has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment. Participants were men (n = 1654) enrolled in a prospective study of PCa development. Genotypes ...[more]

PMID: 27080480

Similar Datasets

Project description:Zebrafish are easy to breed in a laboratory setting as they are extremely fertile and produce dozens of eggs per set. Because zebrafish eggs and the skin of the early-stage larvae are transparent, their embryos and the hearts and muscles of their larvae can be easily observed. Multiple rapid analyses of heart rate and behavior can be performed on these larvae simultaneously, enabling investigation of the influence of neuroactive substances on abnormal behavior, death, and associated pathogenetic mechanisms. Zebrafish larvae are becoming increasingly popular among researchers and are used in laboratories worldwide to study various vertebrate life phenomena; more experimental systems using zebrafish will undoubtedly be developed in the future. However, based on the available literature, we believe that the conceptualization of a protocol based on scientific evidence is necessary to achieve standardization. We exposed zebrafish larvae at 6-7 days post-fertilization to 50 repeated light-dark stimuli at either 15-min or 5-min intervals. We measured the traveled distance and habituation time through a video tracking apparatus. The traveled distance stabilized after the 16th repetition when the zebrafish were exposed to light-dark stimuli at 15-min intervals and after the 5th repetition when exposed at 5-min intervals. Additionally, at 15-min intervals, the peak of the traveled distance was reached within the first minute in a dark environment, whereas at 5-min intervals, it did not reach the peak even after 5 min. The traveled distance was more stable at 5-min intervals of light/dark stimuli than at 15-min intervals. Therefore, if one acclimatizes zebrafish larvae for 1 h and collects data from the 5th repetition of light/dark stimuli at intervals of 5 min in the light/dark test, a stable traveled distance result can be obtained. The establishment of this standardized method would be beneficial for investigating substances of unknown lethal concentration.

Dataset Information

Population-standardized genetic risk score: the SNP-based method of choice for inherited risk assessment of prostate cancer.

Publications

Population-standardized genetic risk score: the SNP-based method of choice for inherited risk assessment of prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets