多基因遗传风险评分(PRS)在遗传疾病研究中的应用与前景:数据分析方法综述  

Application and Prospects of Polygenic Risk Score(PRS)in Genetic Disease Research:a Review of Data Analysis Methods

作　　者：贺舒欣 喻长顺 贾晓冬 陈建春 闫克强 HE Shu-Xin;YU Chang-Shun;JIA Xiao-Dong;CHEN Jian-Chun;YAN Ke-Qiang(Tianjin Kingmed Center for Clinical Laboratory,Tianjin 300392,China;Tianjin Key Laboratory of Multiomics Precision Diagnosis Technology of Neurological Diseases,Tianjin 300392,China)

机构地区：[1]天津金域医学检验实验室,天津300392 [2]天津市神经系统疾病多组学精准诊断技术重点实验室,天津300392

出　　处：《生物化学与生物物理进展》2024年第8期1797-1808,共12页Progress In Biochemistry and Biophysics

基　　金：天津市科技领军培育企业重大创新项目(22YDPYSY00220)资助。

摘　　要：多基因遗传风险评分(polygenic risk score,PRS)是一种新兴的遗传数据分析方法。该方法通过对个体多个遗传变异位点的综合考虑,对个体复杂疾病的遗传风险进行定量评估,在遗传学领域受到广泛关注,同时该方法的有效性也在临床应用中得到进一步验证。由于PRS的计算涉及大量的基因组数据分析,其模型的数据选择、构建方法以及验证方法均存在较大差异。本综述结合目前已发表的PRS相关研究和算法,对PRS模型以及其应用进行阐述。Lower-cost genotyping technology has promoted the generation of large genetic datasets with the evolving next-generation sequencing technology.The emergence of genome-wide association studies(GWAS)has facilitated researchers’understanding of common complex diseases.GWAS refers to finding the sequence variations present in the human genome and screening out disease-related single nucleotide polymorphisms(SNPs).These SNPs are considered as the basis for assessing the stability of complex diseases.However,a single variation is not sufficient to assess an individual’s risk of disease.Polygenic risk score(PRS)is an emerging genetic data analysis method for quantitatively estimating an individual’s genetic risk for complex diseases by comprehensively considering multiple genetic variation sites.A single-value estimate of an individual’s genetic risk for a certain phenotype can be calculated as the cumulative impact of multiple genetic variants by building a PRS model.The finally expected risk score is weighted by the strength and direction of association of each SNP with the phenotype based on the number of alleles carried by each SNP.With the continuous development of various PRS calculation methods and the constant accumulation of genomic data,PRS has received widespread attention in the field of genetics.So far,quite a few studies at home and abroad have shown that PRS is valuable in risk prediction of different types of human traits or complex diseases,and its effectiveness has been further verified in clinical applications.At present,many studies have established PRS models based on GWAS summary statistics to quantify the genetic risk of susceptibility loci and clinical characteristics on diseases such as lung cancer,breast cancer,coronary heart disease,diabetes and Alzheimer’s disease.The disease-susceptible populations can be recognized through comparing the relative risk and absolute risk of the disease in different risk groups according to the population risk stratification results.Additionally,indiv

关 键 词：多基因遗传风险评分 全基因组关联研究 遗传学 复杂疾病 

分 类 号：R466[医药卫生—临床医学] Q3[生物学—遗传学]