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A note on p-value multiple-testing adjustment for two-step genome-wide gene-environment interactions scans

Lewinger, J. P.; Kawaguchi, E. S.; Gauderman, W. J.

2023-06-28 epidemiology
10.1101/2023.06.27.23291946 medRxiv
Show abstract

Two-step testing has emerged as the leading approach for genome-wide gene-environment interaction scans, providing greater power than standard single-step methods in nearly all plausible scenarios. This gain in power has enabled several recent discoveries in gene-environment interactions. However, despite controlling the genome-wide type I error rate, two-step tests typically lack valid p-values, hindering comparisons with single-step results. We demonstrate how multiple-testing adjusted p-values can be defined for two-step tests using standard multiple-testing theory, and how these can be further scaled to allow valid comparisons with single-step tests.

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