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

2.50
Hdl Handle:
http://hdl.handle.net/11287/604235
Title:
Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants.
Authors:
Pilling, L. C.; Atkins, J. L.; Bowman, K.; Jones, S. E.; Tyrrell, J.; Beaumont, R. N.; Ruth, K. S.; Tuke, M. A.; Yaghootkar, Hanieh; Wood, A. R.; Freathy, Rachel M.; Murray, Anna; Weedon, M.N.; Xue, L.; Lunetta, K.; Murabito, J. M.; Harries, L. W.; Robine, J-M.; Brayne, C.; Kuchel, G. A.; Ferrucci, L.; Frayling, T. M.; Melzer, David
Abstract:
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=5.7x10-3). 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.
Citation:
Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants. 2016 Mar;8(3):547-60
Publisher:
Impact Aging
Journal:
Aging
Issue Date:
23-Mar-2016
URI:
http://hdl.handle.net/11287/604235
PubMed ID:
27015805
Additional Links:
http://www.impactaging.com/full/100930
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text from the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1945-4589
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPilling, L. C.en
dc.contributor.authorAtkins, J. L.en
dc.contributor.authorBowman, K.en
dc.contributor.authorJones, S. E.en
dc.contributor.authorTyrrell, J.en
dc.contributor.authorBeaumont, R. N.en
dc.contributor.authorRuth, K. S.en
dc.contributor.authorTuke, M. A.en
dc.contributor.authorYaghootkar, Haniehen
dc.contributor.authorWood, A. R.en
dc.contributor.authorFreathy, Rachel M.en
dc.contributor.authorMurray, Annaen
dc.contributor.authorWeedon, M.N.en
dc.contributor.authorXue, L.en
dc.contributor.authorLunetta, K.en
dc.contributor.authorMurabito, J. M.en
dc.contributor.authorHarries, L. W.en
dc.contributor.authorRobine, J-M.en
dc.contributor.authorBrayne, C.en
dc.contributor.authorKuchel, G. A.en
dc.contributor.authorFerrucci, L.en
dc.contributor.authorFrayling, T. M.en
dc.contributor.authorMelzer, Daviden
dc.date.accessioned2016-04-01T15:00:09Zen
dc.date.available2016-04-01T15:00:09Zen
dc.date.issued2016-03-23en
dc.identifier.citationHuman longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants. 2016 Mar;8(3):547-60en
dc.identifier.issn1945-4589en
dc.identifier.pmid27015805en
dc.identifier.urihttp://hdl.handle.net/11287/604235en
dc.description.abstractVariation 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=5.7x10-3). 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.en
dc.languageENGen
dc.language.isoenen
dc.publisherImpact Agingen
dc.relation.urlhttp://www.impactaging.com/full/100930en
dc.rightsArchived with thanks to Aging. 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.en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleHuman longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants.en
dc.typeJournal Articleen
dc.identifier.journalAgingen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text from the publisher's site.en
dc.type.versionIn press (epub ahead of print)en

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