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Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E

Drenos, F; Kirkwood, TBL; (2010) Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E. PLOS ONE , 5 (3) , Article e10022. 10.1371/journal.pone.0010022. Green open access

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Abstract

It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible. A gradual increase with each generation of the epsilon 2 and epsilon 3 alleles of the gene at the expense of the epsilon 4 allele was predicted from the model. The epsilon 2 allele frequency was found to increase slightly more rapidly than that for epsilon 3, although there was no statistically significant difference between the two. Our result may explain the recent evolutionary history of the epsilon 2, 3 and 4 alleles of the apolipoprotein E gene and has wider relevance for genes affecting human longevity.

Type: Article
Title: Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0010022
Publisher version: http://dx.doi.org/10.1371/journal.pone.0010022
Language: English
Additional information: © 2010 Drenos, Kirkwood. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The authors thank the Dr Hadwen Trust for financial support (http://www.drhadwentrust.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: CORONARY-HEART-DISEASE, MIDDLE-AGED MEN, E POLYMORPHISM, E GENOTYPE, E GENE, ALZHEIMER-DISEASE, COMMON OUTCOMES, RELATIVE RISK, III HYPERLIPOPROTEINEMIA, CARDIOVASCULAR-DISEASE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: http://discovery.ucl.ac.uk/id/eprint/83235
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