Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants
Luke C. Pilling, Janice L. Atkins, Kirsty Bowman, Samuel E. Jones, Jessica Tyrrell, Robin N. Beaumont, Katherine S. Ruth, Marcus A. Tuke et al.. Aging, 2016-03-23
Topic: Genetics and APOE
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.
Key findings
- In GWAS, a nicotine receptor locus(CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival.
- In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not.
- These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways.
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Study details
- Participants75,244
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 30 of the 58 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 4 / 4 | 75,244 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27015805) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 30 of the 58 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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APA 7th
Pilling, L. C., Atkins, J. L., Bowman, K., Jones, S. E., Tyrrell, J., Beaumont, R. N., et al. (2016). Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants. Aging. https://doi.org/10.18632/aging.100930
Vancouver
Pilling LC, Atkins JL, Bowman K, Jones SE, Tyrrell J, Beaumont RN, et al. Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants. Aging. 2016. doi:10.18632/aging.100930. PMID: 27015805.
BibTeX
@article{pilling2016-27015805,
author = {Pilling, Luke C. and Atkins, Janice L. and Bowman, Kirsty and Jones, Samuel E. and Tyrrell, Jessica and Beaumont, Robin N. and Ruth, Katherine S. and Tuke, Marcus A. and others},
title = {{Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants}},
journal = {Aging},
year = {2016},
doi = {10.18632/aging.100930},
pmid = {27015805},
url = {https://doi.org/10.18632/aging.100930}
}
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