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Article: GATES: A rapid and powerful gene-based association test using extended Simes procedure

TitleGATES: A rapid and powerful gene-based association test using extended Simes procedure
Authors
Issue Date2011
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2011, v. 88 n. 3, p. 283-293 How to Cite?
AbstractThe gene has been proposed as an attractive unit of analysis for association studies, but a simple yet valid, powerful, and sufficiently fast method of evaluating the statistical significance of all genes in large, genome-wide datasets has been lacking. Here we propose the use of an extended Simes test that integrates functional information and association evidence to combine the p values of the single nucleotide polymorphisms within a gene to obtain an overall p value for the association of the entire gene. Our computer simulations demonstrate that this test is more powerful than the SNP-based test, offers effective control of the type 1 error rate regardless of gene size and linkage-disequilibrium pattern among markers, and does not need permutation or simulation to evaluate empirical significance. Its statistical power in simulated data is at least comparable, and often superior, to that of several alternative gene-based tests. When applied to real genome-wide association study (GWAS) datasets on Crohn disease, the test detected more significant genes than SNP-based tests and alternative gene-based tests. The proposed test, implemented in an open-source package, has the potential to identify additional novel disease-susceptibility genes for complex diseases from large GWAS datasets. © 2011 The American Society of Human Genetics.
Persistent Identifierhttp://hdl.handle.net/10722/135395
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilGRF HKU 774707
European CommunityHEALTH-F2-2009-241909
University of Hong Kong Strategic Research Theme on Genomics
HKU 201007176166
Funding Information:

We are grateful to Mark J. Daly for sharing data on CD.30 This work was funded by Hong Kong Research Grants Council GRF HKU 774707, the European Community's Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI), the Small Project Funding HKU 201007176166, and The University of Hong Kong Strategic Research Theme on Genomics. We also thank two anonymous reviewers for their useful comments, which improved this paper significantly.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, MXen_HK
dc.contributor.authorGui, HSen_HK
dc.contributor.authorKwan, JSHen_HK
dc.contributor.authorSham, PCen_HK
dc.date.accessioned2011-07-27T01:34:42Z-
dc.date.available2011-07-27T01:34:42Z-
dc.date.issued2011en_HK
dc.identifier.citationAmerican Journal Of Human Genetics, 2011, v. 88 n. 3, p. 283-293en_HK
dc.identifier.issn0002-9297en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135395-
dc.description.abstractThe gene has been proposed as an attractive unit of analysis for association studies, but a simple yet valid, powerful, and sufficiently fast method of evaluating the statistical significance of all genes in large, genome-wide datasets has been lacking. Here we propose the use of an extended Simes test that integrates functional information and association evidence to combine the p values of the single nucleotide polymorphisms within a gene to obtain an overall p value for the association of the entire gene. Our computer simulations demonstrate that this test is more powerful than the SNP-based test, offers effective control of the type 1 error rate regardless of gene size and linkage-disequilibrium pattern among markers, and does not need permutation or simulation to evaluate empirical significance. Its statistical power in simulated data is at least comparable, and often superior, to that of several alternative gene-based tests. When applied to real genome-wide association study (GWAS) datasets on Crohn disease, the test detected more significant genes than SNP-based tests and alternative gene-based tests. The proposed test, implemented in an open-source package, has the potential to identify additional novel disease-susceptibility genes for complex diseases from large GWAS datasets. © 2011 The American Society of Human Genetics.en_HK
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_HK
dc.relation.ispartofAmerican Journal of Human Geneticsen_HK
dc.subject.meshCrohn Disease - geneticsen_US
dc.subject.meshDatabases, Geneticen_US
dc.subject.meshGenetic Association Studies - methodsen_US
dc.subject.meshPolymorphism, Single Nucleotide - geneticsen_US
dc.subject.meshReproducibility of Resultsen_US
dc.titleGATES: A rapid and powerful gene-based association test using extended Simes procedureen_HK
dc.typeArticleen_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.description.naturelink_to_OA_fulltext-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.ajhg.2011.01.019en_HK
dc.identifier.pmid21397060-
dc.identifier.pmcidPMC3059433en_US
dc.identifier.scopuseid_2-s2.0-79952467494en_HK
dc.identifier.hkuros185981en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952467494&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume88en_HK
dc.identifier.issue3en_HK
dc.identifier.spage283en_HK
dc.identifier.epage293en_HK
dc.identifier.eissn1537-6605-
dc.identifier.isiWOS:000288589000006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, MX=35205389900en_HK
dc.identifier.scopusauthoridGui, HS=16645619300en_HK
dc.identifier.scopusauthoridKwan, JSH=37063349600en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.citeulike10089681-

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