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A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies

BACKGROUND: Researchers may embark on a genome-wide association study before fully investigating candidate regions which have been reported to produce evidence to suggest that they harbour susceptibility loci. If the genome wide study had not been carried out then results which demonstrated only mod...

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Autores principales: Curtis, David, Vine, Anna E, Knight, Jo
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1872032/
https://www.ncbi.nlm.nih.gov/pubmed/17490491
http://dx.doi.org/10.1186/1471-2156-8-20
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author Curtis, David
Vine, Anna E
Knight, Jo
author_facet Curtis, David
Vine, Anna E
Knight, Jo
author_sort Curtis, David
collection PubMed
description BACKGROUND: Researchers may embark on a genome-wide association study before fully investigating candidate regions which have been reported to produce evidence to suggest that they harbour susceptibility loci. If the genome wide study had not been carried out then results which demonstrated only modest statistical significance from candidate regions would be judged to be of interest and would stimulate further investigation. However if hundreds of thousands of markers are typed then inevitably very large numbers of such results will occur by chance and those from candidate regions may attract no special attention. RESULTS: An approach is proposed in which differential treatment is afforded to markers from candidate regions and from those that are routinely typed in the context of a genome wide scan. Different prior probabilities are assigned to the two types of marker. A likelihood ratio is derived from the reported p value for each marker, calculated as LR = e(chiinv(1,p)/2), and the posterior odds in favour of a true positive association are obtained. These odds can be used to rank the markers with a view to suggesting the regions in which further genotyping is indicated. We suggest that prior probabilities be specified such that a candidate marker significant at p = 0.01 and a routine marker significant at p = 0.00001 will yield similar values for the posterior odds. We show that this can be achieved by setting a value for prior probability of association to 0.1 for candidate markers and to 0.00018 for routine markers. CONCLUSION: It is essential that formal procedures be adopted in order to avoid modestly positively results from candidate regions being swamped by the huge number of nominally significant results which will be obtained when very many markers are genotyped. Software to carry out the conversion from p values to posterior odds is available from .
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spelling pubmed-18720322007-05-18 A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies Curtis, David Vine, Anna E Knight, Jo BMC Genet Methodology Article BACKGROUND: Researchers may embark on a genome-wide association study before fully investigating candidate regions which have been reported to produce evidence to suggest that they harbour susceptibility loci. If the genome wide study had not been carried out then results which demonstrated only modest statistical significance from candidate regions would be judged to be of interest and would stimulate further investigation. However if hundreds of thousands of markers are typed then inevitably very large numbers of such results will occur by chance and those from candidate regions may attract no special attention. RESULTS: An approach is proposed in which differential treatment is afforded to markers from candidate regions and from those that are routinely typed in the context of a genome wide scan. Different prior probabilities are assigned to the two types of marker. A likelihood ratio is derived from the reported p value for each marker, calculated as LR = e(chiinv(1,p)/2), and the posterior odds in favour of a true positive association are obtained. These odds can be used to rank the markers with a view to suggesting the regions in which further genotyping is indicated. We suggest that prior probabilities be specified such that a candidate marker significant at p = 0.01 and a routine marker significant at p = 0.00001 will yield similar values for the posterior odds. We show that this can be achieved by setting a value for prior probability of association to 0.1 for candidate markers and to 0.00018 for routine markers. CONCLUSION: It is essential that formal procedures be adopted in order to avoid modestly positively results from candidate regions being swamped by the huge number of nominally significant results which will be obtained when very many markers are genotyped. Software to carry out the conversion from p values to posterior odds is available from . BioMed Central 2007-05-10 /pmc/articles/PMC1872032/ /pubmed/17490491 http://dx.doi.org/10.1186/1471-2156-8-20 Text en Copyright © 2007 Curtis et al; 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
Curtis, David
Vine, Anna E
Knight, Jo
A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
title A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
title_full A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
title_fullStr A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
title_full_unstemmed A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
title_short A pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
title_sort pragmatic suggestion for dealing with results for candidate genes obtained from genome wide association studies
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1872032/
https://www.ncbi.nlm.nih.gov/pubmed/17490491
http://dx.doi.org/10.1186/1471-2156-8-20
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