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Article: HYST: A hybrid set-based test for genome-wide association studies, with application to protein-protein interaction-based association analysis

TitleHYST: A hybrid set-based test for genome-wide association studies, with application to protein-protein interaction-based association analysis
Authors
Issue Date2012
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2012, v. 91 n. 3, p. 478-488 How to Cite?
AbstractThe extended Simes' test (known as GATES) and scaled chi-square test were proposed to combine a set of dependent genome-wide association signals at multiple single-nucleotide polymorphisms (SNPs) for assessing the overall significance of association at the gene or pathway levels. The two tests use different strategies to combine association p values and can outperform each other when the number of and linkage disequilibrium between SNPs vary. In this paper, we introduce a hybrid set-based test (HYST) combining the two tests for genome-wide association studies (GWASs). We describe how HYST can be used to evaluate statistical significance for association at the protein-protein interaction (PPI) level in order to increase power for detecting disease-susceptibility genes of moderate effect size. Computer simulations demonstrated that HYST had a reasonable type 1 error rate and was generally more powerful than its parents and other alternative tests to detect a PPI pair where both genes are associated with the disease of interest. We applied the method to three complex disease GWAS data sets in the public domain; the method detected a number of highly connected significant PPI pairs involving multiple confirmed disease-susceptibility genes not found in the SNP- and gene-based association analyses. These results indicate that HYST can be effectively used to examine a collection of predefined SNP sets based on prior biological knowledge for revealing additional disease-predisposing genes of modest effects in GWASs. © 2012 The American Society of Human Genetics.
Persistent Identifierhttp://hdl.handle.net/10722/175992
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, MXen_US
dc.contributor.authorKwan, JSHen_US
dc.contributor.authorSham, PCen_US
dc.date.accessioned2012-11-26T09:03:33Z-
dc.date.available2012-11-26T09:03:33Z-
dc.date.issued2012en_US
dc.identifier.citationAmerican Journal Of Human Genetics, 2012, v. 91 n. 3, p. 478-488en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttp://hdl.handle.net/10722/175992-
dc.description.abstractThe extended Simes' test (known as GATES) and scaled chi-square test were proposed to combine a set of dependent genome-wide association signals at multiple single-nucleotide polymorphisms (SNPs) for assessing the overall significance of association at the gene or pathway levels. The two tests use different strategies to combine association p values and can outperform each other when the number of and linkage disequilibrium between SNPs vary. In this paper, we introduce a hybrid set-based test (HYST) combining the two tests for genome-wide association studies (GWASs). We describe how HYST can be used to evaluate statistical significance for association at the protein-protein interaction (PPI) level in order to increase power for detecting disease-susceptibility genes of moderate effect size. Computer simulations demonstrated that HYST had a reasonable type 1 error rate and was generally more powerful than its parents and other alternative tests to detect a PPI pair where both genes are associated with the disease of interest. We applied the method to three complex disease GWAS data sets in the public domain; the method detected a number of highly connected significant PPI pairs involving multiple confirmed disease-susceptibility genes not found in the SNP- and gene-based association analyses. These results indicate that HYST can be effectively used to examine a collection of predefined SNP sets based on prior biological knowledge for revealing additional disease-predisposing genes of modest effects in GWASs. © 2012 The American Society of Human Genetics.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.titleHYST: A hybrid set-based test for genome-wide association studies, with application to protein-protein interaction-based association analysisen_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.ajhg.2012.08.004en_US
dc.identifier.pmid22958900-
dc.identifier.pmcidPMC3511992-
dc.identifier.scopuseid_2-s2.0-84866127370en_US
dc.identifier.hkuros224359-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84866127370&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume91en_US
dc.identifier.issue3en_US
dc.identifier.spage478en_US
dc.identifier.epage488en_US
dc.identifier.isiWOS:000308683100008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLi, MX=35205389900en_US
dc.identifier.scopusauthoridKwan, JSH=37063349600en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US

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