Abstract
We propose an omnibus family-based association test (MFBAT) that can be applied to multiple markers and multiple phenotypes and that has only one degree of freedom. The proposed test statistic extends current FBAT methodology to incorporate multiple markers as well as multiple phenotypes. Using simulation studies, power estimates for the proposed methodology are compared with the standard methodologies. On the basis of these simulations, we find that MFBAT substantially outperforms other methods, including haplotypic approaches and doing multiple tests with single single-nucleotide polymorphisms (SNPs) and single phenotypes. The practical relevance of the approach is illustrated by an application to asthma in which SNP/phenotype combinations are identified and reach overall significance that would not have been identified using other approaches. This methodology is directly applicable to cases in which there are multiple SNPs, such as candidate gene studies, cases in which there are multiple phenotypes, such as expression data, and cases in which there are multiple phenotypes and genotypes, such as genome-wide association studies that incorporate expression profiles as phenotypes. This program is available in the PBAT analysis package.
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Acknowledgements
We thank all subjects for their ongoing participation in this study. We acknowledge the CAMP investigators and research team, supported by NHLBI, for collection of CAMP Genetic Ancillary Study data. All work on data collected from the CAMP Genetic Ancillary Study was conducted at the Channing Laboratory of the Brigham and Women's Hospital under appropriate CAMP policies and human subject's protections. The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, P01 HL083069, R01 HL 086601, and T32 HL07427 from the National Heart, Lung and Blood Institute and the National Institute of Health. We would also like to acknowledge the support from the following grants: R01MH081862, P01 HL083069, U01 HL065899.
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Lasky-Su, J., Murphy, A., McQueen, M. et al. An omnibus test for family-based association studies with multiple SNPs and multiple phenotypes. Eur J Hum Genet 18, 720–725 (2010). https://doi.org/10.1038/ejhg.2009.221
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DOI: https://doi.org/10.1038/ejhg.2009.221
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