Euesden Jack, Lewis Cathryn M, O'Reilly Paul F
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Bioinformatics. 2015 May 1;31(9):1466-8. doi: 10.1093/bioinformatics/btu848. Epub 2014 Dec 29.
A polygenic risk score (PRS) is a sum of trait-associated alleles across many genetic loci, typically weighted by effect sizes estimated from a genome-wide association study. The application of PRS has grown in recent years as their utility for detecting shared genetic aetiology among traits has become appreciated; PRS can also be used to establish the presence of a genetic signal in underpowered studies, to infer the genetic architecture of a trait, for screening in clinical trials, and can act as a biomarker for a phenotype. Here we present the first dedicated PRS software, PRSice ('precise'), for calculating, applying, evaluating and plotting the results of PRS. PRSice can calculate PRS at a large number of thresholds ("high resolution") to provide the best-fit PRS, as well as provide results calculated at broad P-value thresholds, can thin Single Nucleotide Polymorphisms (SNPs) according to linkage disequilibrium and P-value or use all SNPs, handles genotyped and imputed data, can calculate and incorporate ancestry-informative variables, and can apply PRS across multiple traits in a single run. We exemplify the use of PRSice via application to data on schizophrenia, major depressive disorder and smoking, illustrate the importance of identifying the best-fit PRS and estimate a P-value significance threshold for high-resolution PRS studies.
PRSice is written in R, including wrappers for bash data management scripts and PLINK-1.9 to minimize computational time. PRSice runs as a command-line program with a variety of user-options, and is freely available for download from http://PRSice.info
jack.euesden@kcl.ac.uk or paul.oreilly@kcl.ac.uk
Supplementary data are available at Bioinformatics online.
多基因风险评分（PRS）是多个基因位点上与性状相关的等位基因之和，通常根据全基因组关联研究估计的效应大小进行加权。近年来，PRS的应用不断增加，因为其在检测性状间共享遗传病因方面的效用已得到认可；PRS还可用于在功效不足的研究中确定遗传信号的存在、推断性状的遗传结构、用于临床试验筛选，并可作为一种表型的生物标志物。在此，我们展示了首个专门用于计算、应用、评估和绘制PRS结果的软件PRSice（“精确”）。PRSice可以在大量阈值（“高分辨率”）下计算PRS以提供最佳拟合的PRS，还能提供在宽泛P值阈值下计算的结果，可以根据连锁不平衡和P值对单核苷酸多态性（SNP）进行筛选或使用所有SNP，处理基因分型和推算数据，可以计算并纳入祖先信息变量，并且可以在一次运行中对多个性状应用PRS。我们通过将PRSice应用于精神分裂症、重度抑郁症和吸烟的数据来举例说明其用途，阐述了识别最佳拟合PRS的重要性，并估计了高分辨率PRS研究的P值显著性阈值。
PRSice是用R编写的，包括用于bash数据管理脚本和PLINK - 1.9的包装器，以尽量减少计算时间。PRSice作为一个具有多种用户选项的命令行程序运行，可从http://PRSice.info免费下载。
jack.euesden@kcl.ac.uk或paul.oreilly@kcl.ac.uk
补充数据可在《生物信息学》在线获取。
