A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
Abstract
BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity.
METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective
cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular
Health Study, the Framingham Heart Study, and the Rotterdam Study participating in
the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.
Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison
group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955).
In a second discovery stage, additional genotyping was conducted in the Leiden Longevity
Study cohort and the Danish 1905 cohort. RESULTS: There were 273 single-nucleotide
polymorphism (SNP) associations with p < .0001, but none reached the prespecified
significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent
signals, and 16 of these SNPs were successfully genotyped in the second discovery
stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined
meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1
(chromosome 10), a well-conserved gene involved in regulation of cellular proliferation.
The minor allele was associated with lower odds of survival past age 90 (odds ratio
= 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3)
and PAPPA2 were not strengthened in the second stage. CONCLUSION: Survival studies
of larger size or more extreme or specific phenotypes may support or refine these
initial findings.
Type
Journal articleSubject
AdultAge Factors
Aged
Aged, 80 and over
Alleles
Cohort Studies
Confidence Intervals
Female
Genome-Wide Association Study
Genotype
Humans
Longevity
Male
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
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https://hdl.handle.net/10161/14791Published Version (Please cite this version)
10.1093/gerona/glq028Publication Info
Newman, Anne B; Walter, Stefan; Lunetta, Kathryn L; Garcia, Melissa E; Slagboom, P
Eline; Christensen, Kaare; ... Murabito, Joanne M (2010). A meta-analysis of four genome-wide association studies of survival to age 90 years
or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
J Gerontol A Biol Sci Med Sci, 65(5). pp. 478-487. 10.1093/gerona/glq028. Retrieved from https://hdl.handle.net/10161/14791.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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James Walton Vaupel
Research Professor Emeritus in the Sanford School of Public Policy
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