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Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants

Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's dat...

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Autores principales: Pilling, Luke C., Atkins, Janice L., Bowman, Kirsty, Jones, Samuel E., Tyrrell, Jessica, Beaumont, Robin N., Ruth, Katherine S., Tuke, Marcus A., Yaghootkar, Hanieh, Wood, Andrew R., Freathy, Rachel M., Murray, Anna, Weedon, Michael N., Xue, Luting, Lunetta, Kathryn, Murabito, Joanne M., Harries, Lorna W., Robine, Jean-Marie, Brayne, Carol, Kuchel, George A., Ferrucci, Luigi, Frayling, Timothy M., Melzer, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833145/
https://www.ncbi.nlm.nih.gov/pubmed/27015805
http://dx.doi.org/10.18632/aging.100930
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author Pilling, Luke C.
Atkins, Janice L.
Bowman, Kirsty
Jones, Samuel E.
Tyrrell, Jessica
Beaumont, Robin N.
Ruth, Katherine S.
Tuke, Marcus A.
Yaghootkar, Hanieh
Wood, Andrew R.
Freathy, Rachel M.
Murray, Anna
Weedon, Michael N.
Xue, Luting
Lunetta, Kathryn
Murabito, Joanne M.
Harries, Lorna W.
Robine, Jean-Marie
Brayne, Carol
Kuchel, George A.
Ferrucci, Luigi
Frayling, Timothy M.
Melzer, David
author_facet Pilling, Luke C.
Atkins, Janice L.
Bowman, Kirsty
Jones, Samuel E.
Tyrrell, Jessica
Beaumont, Robin N.
Ruth, Katherine S.
Tuke, Marcus A.
Yaghootkar, Hanieh
Wood, Andrew R.
Freathy, Rachel M.
Murray, Anna
Weedon, Michael N.
Xue, Luting
Lunetta, Kathryn
Murabito, Joanne M.
Harries, Lorna W.
Robine, Jean-Marie
Brayne, Carol
Kuchel, George A.
Ferrucci, Luigi
Frayling, Timothy M.
Melzer, David
author_sort Pilling, Luke C.
collection PubMed
description Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus (CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival. Less common variants requiring further confirmation were also identified. Offspring of longer lived parents had more protective alleles for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not. Associations between extreme longevity (mother >=98 years, fathers >=95 years, n=1,339) and disease alleles were similar, with an additional association with HDL cholesterol (p=5.7×10-3). These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable.
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spelling pubmed-48331452016-04-20 Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants Pilling, Luke C. Atkins, Janice L. Bowman, Kirsty Jones, Samuel E. Tyrrell, Jessica Beaumont, Robin N. Ruth, Katherine S. Tuke, Marcus A. Yaghootkar, Hanieh Wood, Andrew R. Freathy, Rachel M. Murray, Anna Weedon, Michael N. Xue, Luting Lunetta, Kathryn Murabito, Joanne M. Harries, Lorna W. Robine, Jean-Marie Brayne, Carol Kuchel, George A. Ferrucci, Luigi Frayling, Timothy M. Melzer, David Aging (Albany NY) Research Paper Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus (CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival. Less common variants requiring further confirmation were also identified. Offspring of longer lived parents had more protective alleles for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not. Associations between extreme longevity (mother >=98 years, fathers >=95 years, n=1,339) and disease alleles were similar, with an additional association with HDL cholesterol (p=5.7×10-3). These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable. Impact Journals LLC 2016-03-23 /pmc/articles/PMC4833145/ /pubmed/27015805 http://dx.doi.org/10.18632/aging.100930 Text en Copyright: © 2016 Pilling et al. http://creativecommons.org/licenses/by/2.5/ 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.
spellingShingle Research Paper
Pilling, Luke C.
Atkins, Janice L.
Bowman, Kirsty
Jones, Samuel E.
Tyrrell, Jessica
Beaumont, Robin N.
Ruth, Katherine S.
Tuke, Marcus A.
Yaghootkar, Hanieh
Wood, Andrew R.
Freathy, Rachel M.
Murray, Anna
Weedon, Michael N.
Xue, Luting
Lunetta, Kathryn
Murabito, Joanne M.
Harries, Lorna W.
Robine, Jean-Marie
Brayne, Carol
Kuchel, George A.
Ferrucci, Luigi
Frayling, Timothy M.
Melzer, David
Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
title Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
title_full Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
title_fullStr Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
title_full_unstemmed Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
title_short Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
title_sort human longevity is influenced by many genetic variants: evidence from 75,000 uk biobank participants
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833145/
https://www.ncbi.nlm.nih.gov/pubmed/27015805
http://dx.doi.org/10.18632/aging.100930
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