Journal
AGING-US
Volume 9, Issue 12, Pages 2504-2520Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101334
Keywords
longevity; GWAS; human; genetic; 1417
Categories
Funding
- Medical Research Council [MR/M023095/1]
- National Institute on Aging, U.S. National Institutes of Health
- University of Connecticut Health Center
- National Institute on Aging [NIA U01AG009740, AG09775, AG21079, AG33285]
- Social Security Administration
- Vilas Estate Trust
- National Science Foundation
- Spencer Foundation
- Graduate School of the University of Wisconsin-Madison
- William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
- MRC [MR/M023095/1] Funding Source: UKRI
- Medical Research Council [MR/M023095/1, MC_qA137853] Funding Source: researchfish
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We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers' and fathers' attained age, 10 loci were associated (p<5*10(-8)), including 8 previously identified for traits including survival, Alzheimer's and cardiovascular disease. Of these, 4 were also associated with longest 10% survival (mother's age >= 90 years, father's >= 87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Mother's age at death was associated with 3 additional loci (2 linked to autoimmune conditions), and 8 for fathers only. An attained age genetic risk score associated with parental survival in the US Health and Retirement Study and the Wisconsin Longitudinal Study and with having a centenarian parent (n=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity.
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