EraSOR: a software tool to eliminate inflation caused by sample overlap in polygenic score analyses.

ABSTRACT:

Background

Polygenic risk score (PRS) analyses are now routinely applied across biomedical research. However, as PRS studies grow in size, there is an increased risk of sample overlap between the genome-wide association study (GWAS) from which the PRS is derived and the "target sample," in which PRSs are computed and hypotheses are tested. Despite the wide recognition of the sample overlap problem, its potential impact on the results from PRS studies has not yet been quantified, and no analytical solution has been provided.

Findings

Here, we first conduct a comprehensive investigation into the scale of the sample overlap problem, finding that PRS results can be substantially inflated even in the presence of minimal overlap. Next, we introduce a method and software, EraSOR (E

SUBMITTER: Choi SW 

PROVIDER: S-EPMC10273836 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature