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- Publisher Website: 10.1016/j.ajhg.2012.08.004
- Scopus: eid_2-s2.0-84866127370
- PMID: 22958900
- WOS: WOS:000308683100008
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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
Title | HYST: A hybrid set-based test for genome-wide association studies, with application to protein-protein interaction-based association analysis |
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Authors | |
Issue Date | 2012 |
Publisher | Cell 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/175992 |
ISSN | 2023 Impact Factor: 8.1 2023 SCImago Journal Rankings: 4.516 |
PubMed Central ID | |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Li, MX | en_US |
dc.contributor.author | Kwan, JSH | en_US |
dc.contributor.author | Sham, PC | en_US |
dc.date.accessioned | 2012-11-26T09:03:33Z | - |
dc.date.available | 2012-11-26T09:03:33Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | American Journal Of Human Genetics, 2012, v. 91 n. 3, p. 478-488 | en_US |
dc.identifier.issn | 0002-9297 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/175992 | - |
dc.description.abstract | The 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.language | eng | en_US |
dc.publisher | Cell Press. The Journal's web site is located at http://www.cell.com/AJHG/ | en_US |
dc.relation.ispartof | American Journal of Human Genetics | en_US |
dc.title | HYST: A hybrid set-based test for genome-wide association studies, with application to protein-protein interaction-based association analysis | en_US |
dc.type | Article | en_US |
dc.identifier.email | Sham, PC: pcsham@hku.hk | en_US |
dc.identifier.authority | Sham, PC=rp00459 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1016/j.ajhg.2012.08.004 | en_US |
dc.identifier.pmid | 22958900 | - |
dc.identifier.pmcid | PMC3511992 | - |
dc.identifier.scopus | eid_2-s2.0-84866127370 | en_US |
dc.identifier.hkuros | 224359 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-84866127370&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 91 | en_US |
dc.identifier.issue | 3 | en_US |
dc.identifier.spage | 478 | en_US |
dc.identifier.epage | 488 | en_US |
dc.identifier.isi | WOS:000308683100008 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Li, MX=35205389900 | en_US |
dc.identifier.scopusauthorid | Kwan, JSH=37063349600 | en_US |
dc.identifier.scopusauthorid | Sham, PC=34573429300 | en_US |
dc.identifier.issnl | 0002-9297 | - |