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Article: Association analysis of mild mental impairment using DNA pooling to screen 432 brain-expressed single-nucleotide polymorphisms

TitleAssociation analysis of mild mental impairment using DNA pooling to screen 432 brain-expressed single-nucleotide polymorphisms
Authors
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mp
Citation
Molecular Psychiatry, 2005, v. 10 n. 4, p. 384-392 How to Cite?
AbstractWe hypothesize that mild mental impairment (MMI) represents the low extreme of the same quantitative trait loci (QTLs) that operate throughout the distribution of intelligence. To detect QTLs of small effect size, we employed a direct association strategy by genotyping 432 presumably functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) identified from public databases on DNA pools of 288 cases and 1025 controls. In total, 288 MMI cases were identified by in-home administration of McCarthy Scales of Children's Abilities to 836 twin pairs selected from a community sample of more than 14000 children previously screened for nonverbal cognitive delay using parentally administered tests. Controls were selected from the community sample representing the full range of nonverbal intelligence. SNPs showing at least 7% allele frequency differences between case and control DNA pools were tested for their association with the full range of nonverbal intelligence using five DNA subpools, each representing quintiles of the normal quantitative trait scores from the 1025 controls. SNPs showing linear associations in the expected direction across quintiles using pooled DNA were individually genotyped for the 288 cases and 1025 controls and analysed using standard statistical methods. One SNP (rs1136141) in HSPA8 met these criteria, yielding a significant (P = 0.036) allelic frequency difference between cases and controls for individual genotyping and a significant (P = 0.013) correlation within the control group that accounts for 0.5% of the variance. The present SNP strategy combined with DNA pooling and large samples represents a step towards identifying QTLs of small effect size associated with complex traits in the postgenomic era when all functional polymorphisms will be known. © 2005 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/175918
ISSN
2015 Impact Factor: 13.314
2015 SCImago Journal Rankings: 6.790
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorButcher, LMen_US
dc.contributor.authorMeaburn, Een_US
dc.contributor.authorDale, PSen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorSchalkwyk, LCen_US
dc.contributor.authorCraig, IWen_US
dc.contributor.authorPlomin, Ren_US
dc.date.accessioned2012-11-26T09:02:28Z-
dc.date.available2012-11-26T09:02:28Z-
dc.date.issued2005en_US
dc.identifier.citationMolecular Psychiatry, 2005, v. 10 n. 4, p. 384-392en_US
dc.identifier.issn1359-4184en_US
dc.identifier.urihttp://hdl.handle.net/10722/175918-
dc.description.abstractWe hypothesize that mild mental impairment (MMI) represents the low extreme of the same quantitative trait loci (QTLs) that operate throughout the distribution of intelligence. To detect QTLs of small effect size, we employed a direct association strategy by genotyping 432 presumably functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) identified from public databases on DNA pools of 288 cases and 1025 controls. In total, 288 MMI cases were identified by in-home administration of McCarthy Scales of Children's Abilities to 836 twin pairs selected from a community sample of more than 14000 children previously screened for nonverbal cognitive delay using parentally administered tests. Controls were selected from the community sample representing the full range of nonverbal intelligence. SNPs showing at least 7% allele frequency differences between case and control DNA pools were tested for their association with the full range of nonverbal intelligence using five DNA subpools, each representing quintiles of the normal quantitative trait scores from the 1025 controls. SNPs showing linear associations in the expected direction across quintiles using pooled DNA were individually genotyped for the 288 cases and 1025 controls and analysed using standard statistical methods. One SNP (rs1136141) in HSPA8 met these criteria, yielding a significant (P = 0.036) allelic frequency difference between cases and controls for individual genotyping and a significant (P = 0.013) correlation within the control group that accounts for 0.5% of the variance. The present SNP strategy combined with DNA pooling and large samples represents a step towards identifying QTLs of small effect size associated with complex traits in the postgenomic era when all functional polymorphisms will be known. © 2005 Nature Publishing Group All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mpen_US
dc.relation.ispartofMolecular Psychiatryen_US
dc.subject.meshBrain - Physiologyen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshChilden_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshCognition Disorders - Geneticsen_US
dc.subject.meshDna - Geneticsen_US
dc.subject.meshGene Poolen_US
dc.subject.meshGenetic Testingen_US
dc.subject.meshGenome, Humanen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHsc70 Heat-Shock Proteinsen_US
dc.subject.meshHsp70 Heat-Shock Proteins - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshIntelligence - Geneticsen_US
dc.subject.meshNerve Tissue Proteins - Genetics - Metabolismen_US
dc.subject.meshOligonucleotide Array Sequence Analysis - Methodsen_US
dc.subject.meshPolymorphism, Single Nucleotide - Geneticsen_US
dc.subject.meshQuantitative Trait Locien_US
dc.subject.meshReference Valuesen_US
dc.titleAssociation analysis of mild mental impairment using DNA pooling to screen 432 brain-expressed single-nucleotide polymorphismsen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.mp.4001589en_US
dc.identifier.pmid15452586-
dc.identifier.scopuseid_2-s2.0-16844367873en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-16844367873&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue4en_US
dc.identifier.spage384en_US
dc.identifier.epage392en_US
dc.identifier.isiWOS:000228007600010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridButcher, LM=8901700200en_US
dc.identifier.scopusauthoridMeaburn, E=7801402004en_US
dc.identifier.scopusauthoridDale, PS=7101987679en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridSchalkwyk, LC=7003409002en_US
dc.identifier.scopusauthoridCraig, IW=7102548208en_US
dc.identifier.scopusauthoridPlomin, R=36050187200en_US
dc.identifier.citeulike4195311-

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