Related Experiment Video
Updated: May 21, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
Published on: June 23, 2012
Statistical tests for detecting rare variants using variance-stabilising transformations
1Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA. kai-wang@uiowa.edu
Abstract:
Next generation sequencing holds great promise for detecting rare variants underlying complex human traits. Due to their extremely low allele frequencies, the normality approximation for a proportion no longer works well. The Fisher's exact method appears to be suitable but it is conservative. We investigate the utility of various variance-stabilising transformations in single marker association analysis on rare variants. Unlike a proportion itself, the variance of the transformed proportions no longer depends on the proportion, making application of such transformations to rare variant association analysis extremely appealing. Simulation studies demonstrate that tests based on such transformations are more powerful than the Fisher's exact test while controlling for type I error rate. Based on theoretical considerations and results from simulation studies, we recommend the test based on the Anscombe transformation over tests with other transformations.
Related Concept Videos
Significance Testing: Overview
Testing a Claim about Standard Deviation
The hypothesis testing for the claim of population standard deviation (or variance) requires the data and samples to be random and unbiased. The population distribution also must be normal. There is no specific requirement on the sample size as the estimation is based on the chi-square distribution.
As a first step, the hypothesis (null and alternative) concerning the claim about...
Statistical Methods to Analyze Parametric Data: Student t-Test and Goodness-of-Fit Test
The Student's t-test is a statistical test that examines if there is a statistically significant difference between the means of two groups. This test is instrumental when dealing with data...
Friedman Two-way Analysis of Variance by Ranks
Statistical Inference Techniques in Hypothesis Testing: Parametric Versus Nonparametric Data
Parametric statistics, as the name suggests, assumes that data follow a specific distribution, often a normal distribution. This assumption enables robust hypothesis testing and estimation. Parametric methods, like the Student's t-test or Goodness-of-fit test, are frequently employed in biostatistics due to their robustness. For instance, comparing...
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

