Year: 2014
Type: article
Abstract: We are now well into the sequencing era of genetic analysis, and methods to investigate rare variants associated with disease remain in high demand. Currently, the more common rare variant analysis methods are burden tests and variance component tests. This report introduces a burden test known as the modified replication based sum statistic and evaluates its performance, and the performance of other common burden and variance component tests under the setting of a small sample size (103 total cases and controls) using the Genetic Analysis Workshop 18 simulated data with complete knowledge of the simulation model. Specifically we look at the variable threshold sum statistic, replication-based sum statistics, the C-alpha, and sequence kernel association test. Using minor allele frequency thresholds of less than 0.05, we find that the modified replication based sum statistic is competitive with all methods and that using 103 individuals leads to all methods being vastly underpowered. Much larger sample sizes are needed to confidently find truly associated genes.
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, NIDDM Susceptibility Genes in Mexican Americans, Genetics of Gallbladder Disease in Mexican Americans, G725404114, Genetic Analysis of Common Diseases: An Evaluation, Novel Statistical methods for DNA Sequencing Data, and applications to Autism., G9000043073, G9000183473, G9000244037
OpenAlex ID: W1992661466