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Article: Planning genetic studies in human stroke: Sample size estimates based on family history data

TitlePlanning genetic studies in human stroke: Sample size estimates based on family history data
Authors
Issue Date2002
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurology.org
Citation
Neurology, 2002, v. 58 n. 10, p. 1483-1488 How to Cite?
AbstractBackground: Identification of stroke risk genes in humans has relied on case-control methods to determine the association between candidate genes and disease. Alternative approaches include linkage analysis using affected sibling pairs, transmission disequilibrium testing (TDT), and sibling TDT (S-TDT). Despite theoretical benefits, the feasibility of these methods in stroke remains unknown. Methods: Family history was determined in 727 patients with ischemic stroke and 623 control subjects. These data were used to estimate the number of stroke patients required for the different study designs. Results: A family history of any stroke occurring at ≤65 years was an independent risk factor for ischemic stroke at all ages (OR 1.47, 95% CI 1.0]2 to 2.12, p = 0.04) and a stronger risk factor for young (≤65 years) ischemic stroke (OR 2.25, 95% CI 1.43 to 3.55, p < 0.0001). For early-onset ischemic stroke, the sibling risk ratio was estimated to be 3.08. Assuming three major stroke loci, collection of 953 affected sibling pairs (both ≤65 years) would be needed for a linkage study, and 115,472 ischemic stroke patients would have to be screened to achieve this sample size from the authors' population. The predicted sample sizes for association studies to detect a gene conferring an OR of 2.0 were case-control methodology (414), TDT (414), and S-TDT (617), which would require screening of 820, 31,680, and 3,062 cases. Conclusion: Alternative genetic approaches are feasible, but TDT and linkage studies using the affected sib-pair methodology may require large multicenter collaborations. S-TDT approaches appear more practical. These estimates will aid in planning of such studies.
Persistent Identifierhttp://hdl.handle.net/10722/175881
ISSN
2015 Impact Factor: 8.166
2015 SCImago Journal Rankings: 3.691
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHassan, Aen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorMarkus, HSen_US
dc.date.accessioned2012-11-26T09:02:08Z-
dc.date.available2012-11-26T09:02:08Z-
dc.date.issued2002en_US
dc.identifier.citationNeurology, 2002, v. 58 n. 10, p. 1483-1488en_US
dc.identifier.issn0028-3878en_US
dc.identifier.urihttp://hdl.handle.net/10722/175881-
dc.description.abstractBackground: Identification of stroke risk genes in humans has relied on case-control methods to determine the association between candidate genes and disease. Alternative approaches include linkage analysis using affected sibling pairs, transmission disequilibrium testing (TDT), and sibling TDT (S-TDT). Despite theoretical benefits, the feasibility of these methods in stroke remains unknown. Methods: Family history was determined in 727 patients with ischemic stroke and 623 control subjects. These data were used to estimate the number of stroke patients required for the different study designs. Results: A family history of any stroke occurring at ≤65 years was an independent risk factor for ischemic stroke at all ages (OR 1.47, 95% CI 1.0]2 to 2.12, p = 0.04) and a stronger risk factor for young (≤65 years) ischemic stroke (OR 2.25, 95% CI 1.43 to 3.55, p < 0.0001). For early-onset ischemic stroke, the sibling risk ratio was estimated to be 3.08. Assuming three major stroke loci, collection of 953 affected sibling pairs (both ≤65 years) would be needed for a linkage study, and 115,472 ischemic stroke patients would have to be screened to achieve this sample size from the authors' population. The predicted sample sizes for association studies to detect a gene conferring an OR of 2.0 were case-control methodology (414), TDT (414), and S-TDT (617), which would require screening of 820, 31,680, and 3,062 cases. Conclusion: Alternative genetic approaches are feasible, but TDT and linkage studies using the affected sib-pair methodology may require large multicenter collaborations. S-TDT approaches appear more practical. These estimates will aid in planning of such studies.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurology.orgen_US
dc.relation.ispartofNeurologyen_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 And Overen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshConfidence Intervalsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Linkage - Geneticsen_US
dc.subject.meshGenetic Testing - Methodsen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibrium - Geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNuclear Familyen_US
dc.subject.meshOdds Ratioen_US
dc.subject.meshPedigreeen_US
dc.subject.meshRisk Factorsen_US
dc.subject.meshSample Sizeen_US
dc.subject.meshStroke - Epidemiology - Geneticsen_US
dc.titlePlanning genetic studies in human stroke: Sample size estimates based on family history dataen_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.pmid12034783-
dc.identifier.scopuseid_2-s2.0-0037188369en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037188369&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume58en_US
dc.identifier.issue10en_US
dc.identifier.spage1483en_US
dc.identifier.epage1488en_US
dc.identifier.isiWOS:000175794700008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridHassan, A=7402686940en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridMarkus, HS=7102054556en_US

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