An omnibus test for family-based association studies with multiple SNPs and multiple phenotypes |
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Authors: | Jessica Lasky-Su Amy Murphy Matthew B McQueen Scott Weiss Christoph Lange |
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Institution: | 1Channing Laboratory, Brigham and Women''s Hospital, Boston, MA, USA;2Department of Medicine, Harvard Medical School, Boston, MA, USA;3Center for Genomic Medicine, Brigham and Women''s Hospital, Boston, MA, USA;4University of Colorado at Boulder, Boulder, CO, USA;5Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA |
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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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Keywords: | family-based association testing (FBAT) genome-wide association studies FBAT-PC multiple marker multiple phenotypes multiple testing |
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