Using the noninformative families in family-based association tests: a powerful new testing strategy - PubMed (original) (raw)

Using the noninformative families in family-based association tests: a powerful new testing strategy

Christoph Lange et al. Am J Hum Genet. 2003 Oct.

Abstract

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.

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References

Electronic-Database Information

    1. PBAT Web Page, http://www.biosun1.harvard.edu/~clange/pbat.htm (for PBAT software)

References

    1. Abecasis GR, Cardon LR, Cookson WOC (2000) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66:279–292 - PMC - PubMed
    1. DeMeo DL, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird NM, Weiss ST (2002) Univariate and multivariate family based analysis of the arg130gln polymorphism of the IL13 gene in the childhood asthma management program. Genet Epidemiol 23:335–348 - PubMed
    1. Falconer DS, Mackay TFC (1997) Introduction to quantitative genetics. Longman, New York
    1. Childhood Asthma Management Program Research Group (1999) The childhood asthma management program (CAMP): design, rationale, and methods. Control Clin Trials 20:91–120 - PubMed
    1. Laird NM, Horvath S, Xu X (2000) Implementing a unified approach to family based tests of association. Genet Epidemiol Suppl 19:S36–S42 - PubMed

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