The SERPINE2 gene is associated with chronic obstructive pulmonary disease.
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Biomedical subjects
Publications and source records attributed to Dawn DeMeo.
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For genetic association studies with multiple phenotypes, we propose a new strategy for multiple testing with family-based association tests (FBATs). The strategy increases the power by both using all available family data and reducing the number of hypotheses tested while being robust against population admixture and stratification. By use of conditional power calculations, the approach screens all possible null hypotheses without biasing the nominal significance level, and it identifies the subset of phenotypes that has optimal power when tested for association by either univariate or multivariate FBATs. An application of our strategy to an asthma study shows the practical relevance of the proposed methodology. In simulation studies, we compare our testing strategy with standard methodology for family studies. Furthermore, the proposed principle of using all data without biasing the nominal significance in an analysis prior to the computation of the test statistic has broad and powerful applications in many areas of family-based association studies.
We introduce a new powerful nonparametric testing strategy for family-based association studies in which multiple quantitative traits are recorded and the phenotype with the strongest genetic component is not known prior to the analysis. In the first stage, using a population-based test based on the generalized estimating equation approach, we test all recorded phenotypes for association with the marker locus without biasing the nominal significance level of the later family-based analysis. In the second stage the phenotype with the smallest p value is selected and tested by a family-based association test for association with the marker locus. This strategy is robust against population admixture and stratification and does not require any adjustment for multiple testing. We demonstrate the advantages of this testing strategy over standard methodology in a simulation study. The practical importance of our testing strategy is illustrated by applications to the Childhood Asthma Management Program asthma data sets.