A multistep approach to single nucleotide polymorphism–set analysis: an evaluation of power and type I error of gene-based tests of association after pathway-based association tests
Year: 2016
Type: article
Abstract: value summarizing association between the set of rare variants and a phenotype of interest. These methods are often called gene-based, rare variant tests of association because the variants in the set are often all contained within the same gene. A reasonable extension of these approaches involves aggregating variants across an even larger set of variants (eg, all variants contained in genes within a pathway). Testing sets of variants such as pathways for association with a disease phenotype reduces multiple testing penalties, may increase power, and allows for straightforward biological interpretation. However, a significant variant-set association test does not indicate precisely which variants contained within that set are causal. Because pathways often contain many variants, it may be helpful to follow-up significant pathway tests by conducting gene-based tests on each gene in that pathway to narrow in on the region of causal variants. In this paper, we propose such a multistep approach for variant-set analysis that can also account for covariates and complex pedigree structure. We demonstrate this approach on simulated phenotypes from Genetic Analysis Workshop 19. We find generally better power for the multistep approach when compared to a more conventional, single-step approach that simply runs gene-based tests of association on each gene across the genome. Further work is necessary to evaluate the multistep approach on different data sets with different characteristics.
Source: BMC Proceedings
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,290
Awards: Multiethnic Study of Type 2 Diabetes Genes, Identifying T2D Variants by DNA Sequencing in Multiethnic Samples, Identification and Replication of Type 2 Diabetes Genes in Mexican Americans, Discovery of Functional Variants in Type 2 Diabetes Genes in Mexican Americans, Identifying variants causal for Type 2 Diabetes in Major human populations, Analyzing the behavior and interpreting the results of gene based tests of rare variant association, NIDDM Susceptibility Genes in Mexican Americans, Predoctoral Research Training in Statistical Genetics, Genetics of Gallbladder Disease in Mexican Americans, G725404114, Genetic Analysis of Common Diseases: An Evaluation, G9000043073, G9000244037
OpenAlex ID: W2551607724