Evaluation of Nyholt’s Procedure for Multiple Testing Correction
- 1 September 2005
- journal article
- Published by S. Karger AG in Human Heredity
- Vol. 60 (1), 19-25
- https://doi.org/10.1159/000087540
Abstract
A simple method for accounting efficiently for multiple testing of many SNPs in an association study was recently proposed by Nyholt, but its performance was not extensively evaluated. The method involves estimating an 'effective number' of independent tests and then adjusting the smallest observed p value using Sidák's formula based on this number of tests. We sought to carry out an empirical and theoretical evaluation of Nyholt's method. Nyholt's method was applied to a sample of 31 genes typed at a total of 291 SNPs and permutation used to determine the type-I error rate for each gene. Based on our empirical results, we algebraically investigated the effective number of independent tests for a simple model of haplotype block structure. The nominal 5% type I error rate varied from under 3% to over 7%, and was dependent on linkage disequilibrium. Theoretical considerations show further that the method can be very conservative in the presence of haplotype block structure. Although Nyholt's approach may be useful as an exploratory tool, it is not an adequate substitute for permutation tests.Keywords
This publication has 8 references indexed in Scilit:
- Rapid Simulation of P Values for Product Methods and Multiple-Testing Adjustment in Association StudiesAmerican Journal of Human Genetics, 2005
- Efficient Computation of Significance Levels for Multiple Associations in Large Studies of Correlated Data, Including Genomewide Association StudiesAmerican Journal of Human Genetics, 2004
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- A Simple Correction for Multiple Testing for Single-Nucleotide Polymorphisms in Linkage Disequilibrium with Each OtherAmerican Journal of Human Genetics, 2004
- Selection of Genetic Markers for Association Analyses, Using Linkage Disequilibrium and HaplotypesAmerican Journal of Human Genetics, 2003
- The Structure of Haplotype Blocks in the Human GenomeScience, 2002
- A simple correction for multiple comparisons in interval mapping genome scansHeredity, 2001
- A Comparison of Linkage Disequilibrium Measures for Fine-Scale MappingGenomics, 1995