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Article: The future of association studies: Gene-based analysis and replication

TitleThe future of association studies: Gene-based analysis and replication
Authors
Issue Date2004
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2004, v. 75 n. 3, p. 353-362 How to Cite?
AbstractHistorically, association tests were limited to single variants, so that the allele was considered the basic unit for association testing. As marker density increases and indirect approaches are used to assess association through linkage disequilibrium, association is now frequently considered at the haplotypic level. We suggest that there are difficulties in replicating association findings at the single-nucleotide-polymorphism (SNP) or the haplotype level, and we propose a shift toward a gene-based approach in which all common variation within a candidate gene is considered jointly. Inconsistencies arising from population differences are more readily resolved by use of a gene-based approach rather than either a SNP-based or a haplotype-based approach. A gene-based approach captures all of the potential risk-conferring variations; thus, negative findings are subject only to the issue of power. In addition, chance findings due to multiple testing can be readily accounted for by use of a genewide-significance level. Meta-analysis procedures can be formalized for gene-based methods through the combination of P values. It is only a matter of time before all variation within genes is mapped, at which point the gene-based approach will become the natural end point for association analysis and will inform our search for functional variants relevant to disease etiology.
Persistent Identifierhttp://hdl.handle.net/10722/45300
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNeale, BMen_HK
dc.contributor.authorSham, PCen_HK
dc.date.accessioned2007-10-30T06:22:15Z-
dc.date.available2007-10-30T06:22:15Z-
dc.date.issued2004en_HK
dc.identifier.citationAmerican Journal Of Human Genetics, 2004, v. 75 n. 3, p. 353-362en_HK
dc.identifier.issn0002-9297en_HK
dc.identifier.urihttp://hdl.handle.net/10722/45300-
dc.description.abstractHistorically, association tests were limited to single variants, so that the allele was considered the basic unit for association testing. As marker density increases and indirect approaches are used to assess association through linkage disequilibrium, association is now frequently considered at the haplotypic level. We suggest that there are difficulties in replicating association findings at the single-nucleotide-polymorphism (SNP) or the haplotype level, and we propose a shift toward a gene-based approach in which all common variation within a candidate gene is considered jointly. Inconsistencies arising from population differences are more readily resolved by use of a gene-based approach rather than either a SNP-based or a haplotype-based approach. A gene-based approach captures all of the potential risk-conferring variations; thus, negative findings are subject only to the issue of power. In addition, chance findings due to multiple testing can be readily accounted for by use of a genewide-significance level. Meta-analysis procedures can be formalized for gene-based methods through the combination of P values. It is only a matter of time before all variation within genes is mapped, at which point the gene-based approach will become the natural end point for association analysis and will inform our search for functional variants relevant to disease etiology.en_HK
dc.format.extent131076 bytes-
dc.format.extent593678 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/pdf-
dc.languageengen_HK
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.rightsAmerican Journal of Human Genetics. Copyright © University of Chicago Press.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshModels, Geneticen_HK
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshLinkage Disequilibriumen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshVariation (Genetics)en_HK
dc.titleThe future of association studies: Gene-based analysis and replicationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9297&volume=75&issue=3&spage=353&epage=362&date=2004&atitle=The+future+of+association+studies:+gene-based+analysis+and+replicationen_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1086/423901en_HK
dc.identifier.pmid15272419en_HK
dc.identifier.pmcidPMC1182015-
dc.identifier.scopuseid_2-s2.0-4143134235en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4143134235&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume75en_HK
dc.identifier.issue3en_HK
dc.identifier.spage353en_HK
dc.identifier.epage362en_HK
dc.identifier.isiWOS:000223272200001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNeale, BM=7003484514en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.citeulike4238212-

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