The combined effect of SNP-marker and phenotype attributes in genome-wide association studies

The last decade has seen rapid improvements in high-throughput single nucleotide polymorphism (SNP) genotyping technologies that have consequently made genome-wide association studies (GWAS) possible. With tens to hundreds of thousands of SNP markers being tested simultaneously in GWAS, it is impera...

Descripción completa

Detalles Bibliográficos
Autores principales: Chan, E K F, Hawken, R, Reverter, A
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680326/
https://www.ncbi.nlm.nih.gov/pubmed/19076733
http://dx.doi.org/10.1111/j.1365-2052.2008.01816.x
_version_ 1782166942438653952
author Chan, E K F
Hawken, R
Reverter, A
author_facet Chan, E K F
Hawken, R
Reverter, A
author_sort Chan, E K F
collection PubMed
description The last decade has seen rapid improvements in high-throughput single nucleotide polymorphism (SNP) genotyping technologies that have consequently made genome-wide association studies (GWAS) possible. With tens to hundreds of thousands of SNP markers being tested simultaneously in GWAS, it is imperative to appropriately pre-process, or filter out, those SNPs that may lead to false associations. This paper explores the relationships between various SNP genotype and phenotype attributes and their effects on false associations. We show that (i) uniformly distributed ordinal data as well as binary data are more easily influenced, though not necessarily negatively, by differences in various SNP attributes compared with normally distributed data; (ii) filtering SNPs on minor allele frequency (MAF) and extent of Hardy–Weinberg equilibrium (HWE) deviation has little effect on the overall false positive rate; (iii) in some cases, filtering on MAF only serves to exclude SNPs from the analysis without reduction of the overall proportion of false associations; and (iv) HWE, MAF and heterozygosity are all dependent on minor genotype frequency, a newly proposed measure for genotype integrity.
format Text
id pubmed-2680326
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-26803262009-05-15 The combined effect of SNP-marker and phenotype attributes in genome-wide association studies Chan, E K F Hawken, R Reverter, A Anim Genet Articles The last decade has seen rapid improvements in high-throughput single nucleotide polymorphism (SNP) genotyping technologies that have consequently made genome-wide association studies (GWAS) possible. With tens to hundreds of thousands of SNP markers being tested simultaneously in GWAS, it is imperative to appropriately pre-process, or filter out, those SNPs that may lead to false associations. This paper explores the relationships between various SNP genotype and phenotype attributes and their effects on false associations. We show that (i) uniformly distributed ordinal data as well as binary data are more easily influenced, though not necessarily negatively, by differences in various SNP attributes compared with normally distributed data; (ii) filtering SNPs on minor allele frequency (MAF) and extent of Hardy–Weinberg equilibrium (HWE) deviation has little effect on the overall false positive rate; (iii) in some cases, filtering on MAF only serves to exclude SNPs from the analysis without reduction of the overall proportion of false associations; and (iv) HWE, MAF and heterozygosity are all dependent on minor genotype frequency, a newly proposed measure for genotype integrity. Blackwell Publishing Ltd 2008-04 /pmc/articles/PMC2680326/ /pubmed/19076733 http://dx.doi.org/10.1111/j.1365-2052.2008.01816.x Text en Journal compilation © 2009 Stichting International Foundation for Animal Genetics
spellingShingle Articles
Chan, E K F
Hawken, R
Reverter, A
The combined effect of SNP-marker and phenotype attributes in genome-wide association studies
title The combined effect of SNP-marker and phenotype attributes in genome-wide association studies
title_full The combined effect of SNP-marker and phenotype attributes in genome-wide association studies
title_fullStr The combined effect of SNP-marker and phenotype attributes in genome-wide association studies
title_full_unstemmed The combined effect of SNP-marker and phenotype attributes in genome-wide association studies
title_short The combined effect of SNP-marker and phenotype attributes in genome-wide association studies
title_sort combined effect of snp-marker and phenotype attributes in genome-wide association studies
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680326/
https://www.ncbi.nlm.nih.gov/pubmed/19076733
http://dx.doi.org/10.1111/j.1365-2052.2008.01816.x
work_keys_str_mv AT chanekf thecombinedeffectofsnpmarkerandphenotypeattributesingenomewideassociationstudies
AT hawkenr thecombinedeffectofsnpmarkerandphenotypeattributesingenomewideassociationstudies
AT revertera thecombinedeffectofsnpmarkerandphenotypeattributesingenomewideassociationstudies
AT chanekf combinedeffectofsnpmarkerandphenotypeattributesingenomewideassociationstudies
AT hawkenr combinedeffectofsnpmarkerandphenotypeattributesingenomewideassociationstudies
AT revertera combinedeffectofsnpmarkerandphenotypeattributesingenomewideassociationstudies