Improving accuracy in genome-wide association studies: a two-step approach for handling below limit of detection biomarker measurements.

ABSTRACT: Advances in high-throughput technologies enable large-scale studies on genomics and molecular phenotypes. However, the trade-off between quality and quantity reduces assay sensitivity, and several measurements in large-scale proteomics and metabolomics analytes fall below the limit of detection (LOD). If not properly addressed, this may introduce bias in effect estimates. To address this, we conducted a simulation study to evaluate the performance of linear, Tobit, Cox, and logistic modeling in the presence of below-LOD measurements in genome-wide association studies. We identified the optimal strategy as a two-step Linear-Tobit scheme, including rapid screening with linear regression followed by refinement with Tobit regression to retrieve accurate effect estimates. This higher accuracy h

SUBMITTER: Deng YA 

PROVIDER: S-EPMC12754788 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature