Genotype Imputation and PGS Tutorial

This tutorial provides a practical introduction to key steps in modern genetic data analysis, including genotype imputation, genome-wide association studies (GWAS), and polygenic risk score (PGS) calculation.

Using the Michigan Imputation Server (MIS) as the imputation platform, the chapter demonstrates how to process and analyze genetic data in a reproducible workflow — from imputed genotypes to interpretable genetic associations.

You will learn how to:

• Perform and evaluate genotype imputation using the Michigan Imputation Server
• Conduct a GWAS to identify variants associated with phenotypes
• Calculate and visualize polygenic risk scores (PRS) for different trait types

The tutorial concludes with examples of four phenotypes, illustrating how PRS performance varies between binary and continuous traits — ranging from clear genetic signals to weak or absent associations.

This chapter aims to build a solid understanding of the concepts, tools, and interpretation steps that underpin large-scale human genetic studies.