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The role of lipid-related genes, aging-related processes, and environment in healthspan

dc.contributor.author Arbeev, Konstantin
dc.contributor.author Arbeeva, L
dc.contributor.author Culminskaya, IV
dc.contributor.author Kulminski, Alexander
dc.contributor.author Stallard, Eric
dc.contributor.author Ukraintseva, Svetlana
dc.contributor.author Yashin, Anatoli I
dc.date.accessioned 2017-06-08T18:40:48Z
dc.date.available 2017-06-08T18:40:48Z
dc.date.issued 2013
dc.identifier.issn 1474-9718
dc.identifier.uri http://hdl.handle.net/10161/14899
dc.description.abstract The inherent complexity of aging-related traits can temper progress in unraveling the genetic origins of healthspan. We focus on two generations in the Framingham Heart Study, the original (FHS) and offspring (FHSO) cohorts, to determine whether aging-related processes in changing environments can substantially impact the role of lipid-related genes discovered in candidate gene (the apolipoprotein E (APOE) e2/3/4 polymorphism) and genome-wide (the APOB rs1042034 (C/T)) studies, in regulation of total cholesterol (TC) and onset of cardiovascular disease (CVD). We demonstrate that the APOE e4 allele and APOB CC genotype can play detrimental, neutral, and protective sexspecific roles in the etiology of CVD at different ages and in different environments. We document antagonistic roles for the e4 allele in the onset of CVD characterized by detrimental effects at younger ages (RR≤ 75 years = 1.49, P = 7.5×104) and protective effects at older ages (RR76+years = 0.77, P = 0.044) for FHS participants. We found that disregarding the role of aging erroneously nullifies the significant effects of the e4 allele in this sample (RR = 0.92, P = 0.387). The leading biogenetic pathways mediating genetic effects on CVD may be more relevant to lipid metabolism for APOB than APOE. Aging-related processes can modulate the strength of genetic associations with TC in the same individuals at different chronological ages. We found substantial differences in the effects of the same APOE and APOB alleles on CVD and TC across generations. The results suggest that aging-related processes in changing environments may play key roles in the genetics of healthspan. Detailed systemic integrative analyses may substantially advance the progress. © 2013 The Authors. © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
dc.relation.ispartof Aging Cell
dc.relation.isversionof 10.1111/acel.12046
dc.title The role of lipid-related genes, aging-related processes, and environment in healthspan
dc.type Journal article
pubs.begin-page 237
pubs.end-page 246
pubs.issue 2
pubs.organisational-group Center for Population Health & Aging
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Population Research Center
pubs.organisational-group Duke Population Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Sanford School of Public Policy
pubs.organisational-group School of Medicine
pubs.organisational-group Social Science Research Institute
pubs.organisational-group University Institutes and Centers
pubs.volume 12


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