Prior to polygenic scoring, we randomly removed one related individual from pairs with pi-hat greater than 0.2, leaving 66,732 individuals of European genetic ancestry and 12,383 individuals of African genetic ancestry. (Fig. 1a). We generated lipids PGS for these individuals using PRS-CS [31] with weights derived from the transethnic MVP lipid GWAS summary statistics [4]. PGS for CAD (CADPGS) was calculated using SNP weights from CARDIoGRAMplusC4D GWAS summary statistics [32] using PRS-CS. Because the majority of the MVP transethnic sample was European, linkage disequilibrium was modeled using the pre-calculated European panel. PRS-CS is a recently developed Bayesian polygenic prediction method that imposes continuous shrinkage priors on SNP effect sizes (Polygenic Risk Score – Continuous Shrinkage) [31]. These priors can be represented as global-local scale mixtures of normals which allow the model to flexibly adapt to differing genetic architectures and provide substantial computational advantages. The shrinkage parameter was automatically learnt from the data (i.e., using PRS-CS-auto). SNP effect estimates were obtained from GWAS summary statistics and the score was calculated using a linkage disequilibrium reference panel from 503 European samples in the 1000 Genomes Project phase 3 [19]. Although PRS-CS outperformed other polygenic scoring methods across a range of traits in previous experiments, its superiority may not hold across all genetic architectures [31]. We therefore also generated PGS for the European sample using PRSice-2 [33] (Additional file 1) and have automated a pipeline to generate scores across both methods. PGS were scaled to have a mean of zero and SD of one before testing for association with any outcome variables. We validated each score by testing the proportion of trait variability explained by the PGS, controlling for sex, cubic splines of median age (4 knots) across the medical record, and the top 10 principal components to adjust for genetic ancestry (Additional file 3: Fig. S3).

Note: The content above has been extracted from a research article, so it may not display correctly.

Please log in to submit your questions online.
Your question will be posted on the Bio-101 website. We will send your questions to the authors of this protocol and Bio-protocol community members who are experienced with this method. you will be informed using the email address associated with your Bio-protocol account.

We use cookies on this site to enhance your user experience. By using our website, you are agreeing to allow the storage of cookies on your computer.