eprintid: 83235
rev_number: 48
eprint_status: archive
userid: 608
dir: disk0/00/08/32/35
datestamp: 2010-10-18 01:50:50
lastmod: 2022-01-03 23:30:30
status_changed: 2010-10-18 01:50:50
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Drenos, F
creators_name: Kirkwood, TBL
title: Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E
ispublished: pub
divisions: UCL
divisions: B02
divisions: D14
keywords: CORONARY-HEART-DISEASE, MIDDLE-AGED MEN, E POLYMORPHISM, E GENOTYPE, E GENE, ALZHEIMER-DISEASE, COMMON OUTCOMES, RELATIVE RISK, III HYPERLIPOPROTEINEMIA, CARDIOVASCULAR-DISEASE
note: © 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.
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.
date: 2010-04-02
publisher: PUBLIC LIBRARY SCIENCE
official_url: http://dx.doi.org/10.1371/journal.pone.0010022
vfaculties: VFPHS
oa_status: green
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_batch
elements_source: Web of Science
elements_id: 217554
doi: 10.1371/journal.pone.0010022
language_elements: EN
lyricists_name: Drenos, Fotios
lyricists_id: FDREN62
full_text_status: public
publication: PLOS ONE
volume: 5
number: 3
article_number: e10022
pagerange: -
issn: 1932-6203
citation:        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 <https://doi.org/10.1371/journal.pone.0010022>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/83235/1/83235.pdf