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Activity Number:
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248
- Recent Advances in Genetic Association and Gene-Environment Interaction Studies
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Type:
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Contributed
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Date/Time:
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Tuesday, August 9, 2022 : 8:30 AM to 10:20 AM
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Sponsor:
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Section on Statistics in Genomics and Genetics
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Abstract #321035
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Title:
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A Novel Ranked Screening Procedure for Two-Step Hypothesis Testing in Gene-Environment Studies
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Author(s):
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Eric Shinya Kawaguchi* and W. James Gauderman and Juan Pablo Lewinger
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Companies:
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University of Southern California and University of Southern California and University of Southern California
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Keywords:
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gene-environment interactions;
correlation;
power;
multiple testing;
hypothesis testing
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Abstract:
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Genome-wide interaction scans (GWIS) can be performed to identify gene-environment (GxE) interactions; however, these scans typically suffer from low power due to the large multiple hypothesis burden. Two-step hypothesis testing approaches have been developed to improve power for GWIS while retaining the family-wise error rate (FWER) at the nominal level by prioritizing genes for Step 2 GxE testing based on a carefully constructed Step-1 screening procedure. In the context of GWIS, standard methods currently do not consider genetic correlation, which can distort the prioritization of genes and can lead to a loss of power. We propose a data-driven approach to gene prioritization by modifying the Step-1 screening procedure. Our expectation-based ranked screening approach to Step 1 prioritizes genes by binning them based on the p-value distribution. To further improve power and account for genetic correlation, the bin-wise error rate is divided by an estimate for the effective number of independent tests. Numerical results indicate the efficacy of our approach when compared to standard two-step hypothesis testing procedures under a variety of scenarios.
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Authors who are presenting talks have a * after their name.
