A polygenic risk score (PRS) is a score that gives you a genetic risk for something, as calculated using many SNPs at the same time. However, polygenic scores do not provide a baseline or timeframe for the progression of a disease. 60 We define polygenic risk scores, or polygenic scores, as a single value estimate of an 61 individual’s propensity to a phenotype, calculated as a sum of their genome-wide genotypes 62 weighted by corresponding genotype effect sizes – potentially scaled or shrunk – … The default formula for PRS calculation in PLINK is: \[ PRS_j =\frac{ \sum_i^NS_i*G_{ij}}{P*M_j} \] where the effect size of SNP \(i\) is \(S_i\) ; the number of effect alleles observed in sample \(j\) is \(G_{ij}\) ; the ploidy of the sample is \(P\) (is generally 2 for humans); the total number of SNPs included in the PRS is \(N\) ; and the number of non-missing SNPs observed in sample \(j\) is \(M_j\) . This tutorial provides a step-by-step guide to performing basic polygenic risk score (PRS) analyses and accompanies our PRS Guide paper. The tutorial is separated into four main sections and reflects the structure of our guide paper: the first two sections on QC corres… For example, consider two people with high polygenic risk scores for having coronary heart disease. A polygenic risk score tells you how a person’s risk compares to others with a different genetic constitution.
The score is typically calculated as a score for a disease, but it can be used for any trait that is affected by many different SNPs. The aim of this tutorial is to provide a simple introduction to PRS analyses to those new to PRS, while equipping existing users with a better understanding of the processes and implementation "underneath the hood" of popular PRS software.