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Evidence for Non-additive Influence of Single Nucleotide Polymorphisms within the Apolipoprotein E Gene

dc.contributor.authorHamon, S. C.en_US
dc.contributor.authorStengard, J. H.en_US
dc.contributor.authorClark, A. G.en_US
dc.contributor.authorSalomaa, V.en_US
dc.contributor.authorBoerwinkle, Ericen_US
dc.contributor.authorSing, Charles F.en_US
dc.date.accessioned2010-04-01T15:10:25Z
dc.date.available2010-04-01T15:10:25Z
dc.date.issued2004-11en_US
dc.identifier.citationHamon, S. C.; Stengard, J. H.; Clark, A. G.; Salomaa, V.; Boerwinkle, E.; Sing, C. F. (2004). "Evidence for Non-additive Influence of Single Nucleotide Polymorphisms within the Apolipoprotein E Gene." Annals of Human Genetics 68(6): 521-535. <http://hdl.handle.net/2027.42/65641>en_US
dc.identifier.issn0003-4800en_US
dc.identifier.issn1469-1809en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/65641
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15598211&dopt=citationen_US
dc.description.abstractWe analyzed 13 single nucleotide polymorphisms (SNPs) within the apolipoprotein E ( APOE ) gene, to identify pairs of SNPs that interact in a non-additive manner to influence genotypic mean levels of the ApoE protein in blood. An overparameterized general linear model of two-SNP genotype means was applied to data from 456 female and 398 male unrelated European Americans from Rochester, MN, USA. We found statistically significant evidence for non-additivity between SNPs within the male sample, but not within the female sample. We observed nine pairs of SNPs with evidence of non-additivity at the Α= 0.05 level of statistical significance within the male sample, when approximately three were expected by chance. Five of the nine pairs involved three SNPs (560, 624 and 1163) that did not have a statistically significant influence when considered separately in a single-site analysis. Three of the nine pairs involving four SNPs (832, 1998, 3937 and 4951) showed significant evidence for non-additivity in at least one of two other male samples from Jackson, MS, USA and North Karelia, Finland. Although all four of these SNPs had a statistically significant influence in Rochester when considered separately, only SNP 3937 gave a significant result in the other male samples. The four SNPs are located in the promoter, intronic and exonic regions, and 3' to the polyadenylation signal in the APOE gene. Our study suggests that analyses that only consider SNPs located in exons and ignore contexts such as those indexed by gender and population, and disregard non-additivity of SNP effects, may inappropriately model the contribution of a gene to the genetic architecture of a trait that has a complex multifactorial etiology.en_US
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dc.format.extent3110 bytes
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dc.publisherBlackwell Science Ltden_US
dc.rights2004 University College Londonen_US
dc.subject.otherEpistasisen_US
dc.subject.otherNon-additivityen_US
dc.subject.otherAPOEen_US
dc.subject.otherAssociation Studiesen_US
dc.subject.otherInteractionen_US
dc.subject.otherContext Dependencyen_US
dc.titleEvidence for Non-additive Influence of Single Nucleotide Polymorphisms within the Apolipoprotein E Geneen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelGeneticsen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Human Genetics, University of Michigan, Ann Arbor, MI, USAen_US
dc.contributor.affiliationotherDepartment of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, FINLANDen_US
dc.contributor.affiliationotherDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USAen_US
dc.contributor.affiliationotherHuman Genetics Center, University of Texas Health Science Center, Houston, TX, USAen_US
dc.identifier.pmid15598211en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/65641/1/j.1529-8817.2003.00112.x.pdf
dc.identifier.doi10.1046/j.1529-8817.2003.00112.xen_US
dc.identifier.sourceAnnals of Human Geneticsen_US
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