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

dc.contributor.author

Kulminski, Alexander M

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Culminskaya, Irina

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Arbeev, Konstantin G

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Ukraintseva, Svetlana V

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Stallard, Eric

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Arbeeva, Liubov

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Yashin, Anatoli I

dc.date.accessioned

2017-06-08T18:40:48Z

dc.date.available

2017-06-08T18:40:48Z

dc.date.issued

2013

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.identifier.issn

1474-9718

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https://hdl.handle.net/10161/14899

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Wiley

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Aging Cell

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10.1111/acel.12046

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Arbeev, Konstantin G|0000-0002-4195-7832

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237

pubs.end-page

246

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2

pubs.organisational-group

Center for Population Health & Aging

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Duke

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Duke Cancer Institute

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Duke Population Research Center

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Duke Population Research Institute

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Institutes and Centers

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Institutes and Provost's Academic Units

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Sanford School of Public Policy

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School of Medicine

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Social Science Research Institute

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University Institutes and Centers

pubs.volume

12

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