Inflation of polygenic risk scores caused by sample overlap and relatedness: Examples of a major risk of bias.

ABSTRACT: Polygenic risk scores (PRSs) are an important tool for understanding the role of common genetic variants in human disease. Standard best practices recommend that PRSs be analyzed in cohorts that are independent of the genome-wide association study (GWAS) used to derive the scores without sample overlap or relatedness between the two cohorts. However, identifying sample overlap and relatedness can be challenging in an era of GWASs performed by large biobanks and international research consortia. Although most genomics researchers are aware of best practices and theoretical concerns about sample overlap and relatedness between GWAS and PRS cohorts, the prevailing assumption is that the risk of bias is small for very large GWASs. Here, we present two real-world examples demonstrating that sam

SUBMITTER: Ellis CA 

PROVIDER: S-EPMC11393675 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature