PRSice: Polygenic Risk Score software.

PRSice: Polygenic Risk Score software.
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DOI:
10.1093/bioinformatics/btu848
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发表时间:
2015-05-01
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
O'Reilly PF
O'Reilly PF
中科院分区:
其他
文献类型:
--
作者:
Euesden J;Lewis CM;O'Reilly PF

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总结:多基因风险评分(PRS)是许多遗传基因座上与性状相关的等位基因的总和,通常由全基因组关联研究估计的效应大小加权。近年来,PRS的应用越来越多,因为它们用于检测性状之间共享的遗传病因的实用性已经得到赞赏; PRS还可以用于在动力不足的研究中建立遗传信号的存在,推断性状的遗传结构,用于临床试验中的筛选,并且可以作为表型的生物标志物。在这里,我们提出了第一个专用的PRS软件,PRSice(“精确”),用于计算,应用,评估和绘制PRS的结果。PRSice可以在大量阈值下计算PRS(“高分辨率”),以提供最佳拟合PRS,以及提供在宽P值阈值下计算的结果,可以根据连锁不平衡和P值细化单核苷酸多态性(SNP)或使用所有SNP,处理基因分型和插补数据,可以计算和合并祖先信息变量,并且可以在单次运行中跨多个性状应用PRS。我们通过应用于精神分裂症、重度抑郁症和吸烟的数据,验证了PRSice的使用,说明了识别最佳拟合PRS的重要性,并估计了高分辨率PRS研究的P值显著性阈值。可用性和实施:PRSice是用R编写的,包括bash数据管理脚本和PLINK-1.9的包装器,以最大限度地减少计算时间。PRSice作为一个命令行程序运行,有各种用户选项,可以从http://PRSice.info免费下载。联系人:jack. kcl.ac.uk或paul. kcl.ac.uk补充信息:补充数据可以在生物信息学在线获得。
Summary: 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. Availability and implementation: 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 Contact: jack.euesden@kcl.ac.uk or paul.oreilly@kcl.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
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