Pervasive polygenicity of complex traits inflates false positive rates in transcriptome-wide association studies.

ABSTRACT: Transcription-wide association studies (TWAS) and related methods (xWAS) have been widely adopted in genetic studies to understand molecular traits as mediators between genetic variation and disease. However, the effect of polygenicity on the validity of these mediator-trait association tests has largely been overlooked. Given the widespread polygenicity of complex traits, it is necessary to assess the validity and accuracy of these mediator-trait association tests. We found that for highly polygenic target traits, the standard test based on linear regression is inflated, leading to greatly increased false positives rates, especially in large sample sizes. Here, we show the extent of the inflation as a function of the underlying GWAS sample size and polygenic heritability of the target tra

SUBMITTER: Liang Y 

PROVIDER: S-EPMC10614931 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature