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Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions
BACKGROUND: It is well known that the presence of population stratification (PS) may cause the usual test in case-control studies to produce spurious gene-disease associations. However, the impact of the PS and sample selection (SS) is less known. In this paper, we provide a systematic study of the...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280159/ https://www.ncbi.nlm.nih.gov/pubmed/22284162 http://dx.doi.org/10.1186/1471-2156-13-5 |
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author | Cheng, KF Lee, JY |
author_facet | Cheng, KF Lee, JY |
author_sort | Cheng, KF |
collection | PubMed |
description | BACKGROUND: It is well known that the presence of population stratification (PS) may cause the usual test in case-control studies to produce spurious gene-disease associations. However, the impact of the PS and sample selection (SS) is less known. In this paper, we provide a systematic study of the joint effect of PS and SS under a more general risk model containing genetic and environmental factors. We provide simulation results to show the magnitude of the bias and its impact on type I error rate of the usual chi-square test under a wide range of PS level and selection bias. RESULTS: The biases to the estimation of main and interaction effect are quantified and then their bounds derived. The estimated bounds can be used to compute conservative p-values for the association test. If the conservative p-value is smaller than the significance level, we can safely claim that the association test is significant regardless of the presence of PS or not, or if there is any selection bias. We also identify conditions for the null bias. The bias depends on the allele frequencies, exposure rates, gene-environment odds ratios and disease risks across subpopulations and the sampling of the cases and controls. CONCLUSION: Our results show that the bias cannot be ignored even the case and control data were matched in ethnicity. A real example is given to illustrate application of the conservative p-value. These results are useful to the genetic association studies of main and interaction effects. |
format | Online Article Text |
id | pubmed-3280159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32801592012-02-16 Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions Cheng, KF Lee, JY BMC Genet Methodology Article BACKGROUND: It is well known that the presence of population stratification (PS) may cause the usual test in case-control studies to produce spurious gene-disease associations. However, the impact of the PS and sample selection (SS) is less known. In this paper, we provide a systematic study of the joint effect of PS and SS under a more general risk model containing genetic and environmental factors. We provide simulation results to show the magnitude of the bias and its impact on type I error rate of the usual chi-square test under a wide range of PS level and selection bias. RESULTS: The biases to the estimation of main and interaction effect are quantified and then their bounds derived. The estimated bounds can be used to compute conservative p-values for the association test. If the conservative p-value is smaller than the significance level, we can safely claim that the association test is significant regardless of the presence of PS or not, or if there is any selection bias. We also identify conditions for the null bias. The bias depends on the allele frequencies, exposure rates, gene-environment odds ratios and disease risks across subpopulations and the sampling of the cases and controls. CONCLUSION: Our results show that the bias cannot be ignored even the case and control data were matched in ethnicity. A real example is given to illustrate application of the conservative p-value. These results are useful to the genetic association studies of main and interaction effects. BioMed Central 2012-01-27 /pmc/articles/PMC3280159/ /pubmed/22284162 http://dx.doi.org/10.1186/1471-2156-13-5 Text en Copyright ©2012 Cheng and Lee; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methodology Article Cheng, KF Lee, JY Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
title | Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
title_full | Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
title_fullStr | Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
title_full_unstemmed | Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
title_short | Assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
title_sort | assessing the joint effect of population stratification and sample selection in studies of gene-gene (environment) interactions |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280159/ https://www.ncbi.nlm.nih.gov/pubmed/22284162 http://dx.doi.org/10.1186/1471-2156-13-5 |
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