Cargando…

Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study

BACKGROUND: The development of new high-throughput genotyping technologies has allowed fast evaluation of single nucleotide polymorphisms (SNPs) on a genome-wide scale. Several recent genome-wide association studies employing these technologies suggest that panels of SNPs can be a useful tool for pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Statnikov, Alexander, Li, Chun, Aliferis, Constantin F.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978529/
https://www.ncbi.nlm.nih.gov/pubmed/17895998
http://dx.doi.org/10.1371/journal.pone.0000958
_version_ 1782135412706246656
author Statnikov, Alexander
Li, Chun
Aliferis, Constantin F.
author_facet Statnikov, Alexander
Li, Chun
Aliferis, Constantin F.
author_sort Statnikov, Alexander
collection PubMed
description BACKGROUND: The development of new high-throughput genotyping technologies has allowed fast evaluation of single nucleotide polymorphisms (SNPs) on a genome-wide scale. Several recent genome-wide association studies employing these technologies suggest that panels of SNPs can be a useful tool for predicting cancer susceptibility and discovery of potentially important new disease loci. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we undertake a careful examination of the relative significance of genetics, environmental factors, and biases of the data analysis protocol that was used in a previously published genome-wide association study. That prior study reported a nearly perfect discrimination of esophageal cancer patients and healthy controls on the basis of only genetic information. On the other hand, our results strongly suggest that SNPs in this dataset are not statistically linked to the phenotype, while several environmental factors and especially family history of esophageal cancer (a proxy to both environmental and genetic factors) have only a modest association with the disease. CONCLUSIONS/SIGNIFICANCE: The main component of the previously claimed strong discriminatory signal is due to several data analysis pitfalls that in combination led to the strongly optimistic results. Such pitfalls are preventable and should be avoided in future studies since they create misleading conclusions and generate many false leads for subsequent research.
format Text
id pubmed-1978529
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-19785292007-09-26 Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study Statnikov, Alexander Li, Chun Aliferis, Constantin F. PLoS One Research Article BACKGROUND: The development of new high-throughput genotyping technologies has allowed fast evaluation of single nucleotide polymorphisms (SNPs) on a genome-wide scale. Several recent genome-wide association studies employing these technologies suggest that panels of SNPs can be a useful tool for predicting cancer susceptibility and discovery of potentially important new disease loci. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we undertake a careful examination of the relative significance of genetics, environmental factors, and biases of the data analysis protocol that was used in a previously published genome-wide association study. That prior study reported a nearly perfect discrimination of esophageal cancer patients and healthy controls on the basis of only genetic information. On the other hand, our results strongly suggest that SNPs in this dataset are not statistically linked to the phenotype, while several environmental factors and especially family history of esophageal cancer (a proxy to both environmental and genetic factors) have only a modest association with the disease. CONCLUSIONS/SIGNIFICANCE: The main component of the previously claimed strong discriminatory signal is due to several data analysis pitfalls that in combination led to the strongly optimistic results. Such pitfalls are preventable and should be avoided in future studies since they create misleading conclusions and generate many false leads for subsequent research. Public Library of Science 2007-09-26 /pmc/articles/PMC1978529/ /pubmed/17895998 http://dx.doi.org/10.1371/journal.pone.0000958 Text en Statnikov et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Statnikov, Alexander
Li, Chun
Aliferis, Constantin F.
Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study
title Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study
title_full Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study
title_fullStr Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study
title_full_unstemmed Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study
title_short Effects of Environment, Genetics and Data Analysis Pitfalls in an Esophageal Cancer Genome-Wide Association Study
title_sort effects of environment, genetics and data analysis pitfalls in an esophageal cancer genome-wide association study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978529/
https://www.ncbi.nlm.nih.gov/pubmed/17895998
http://dx.doi.org/10.1371/journal.pone.0000958
work_keys_str_mv AT statnikovalexander effectsofenvironmentgeneticsanddataanalysispitfallsinanesophagealcancergenomewideassociationstudy
AT lichun effectsofenvironmentgeneticsanddataanalysispitfallsinanesophagealcancergenomewideassociationstudy
AT aliferisconstantinf effectsofenvironmentgeneticsanddataanalysispitfallsinanesophagealcancergenomewideassociationstudy