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.

Newman, Anne B

Walter, Stefan

Lunetta, Kathryn L

Garcia, Melissa E

Slagboom, P Eline

Christensen, Kaare

Arnold, Alice M

Aspelund, Thor

Aulchenko, Yurii S

Benjamin, Emelia J

Christiansen, Lene

D'Agostino, Ralph B

Fitzpatrick, Annette L

Franceschini, Nora

Glazer, Nicole L

Gudnason, Vilmundur

Hofman, Albert

Kaplan, Robert

Karasik, David

Kelly-Hayes, Margaret

Kiel, Douglas P

Launer, Lenore J

Marciante, Kristin D

Massaro, Joseph M

Miljkovic, Iva

Nalls, Michael A

Hernandez, Dena

Psaty, Bruce M

Rivadeneira, Fernando

Rotter, Jerome

Seshadri, Sudha

Smith, Albert V

Taylor, Kent D

Tiemeier, Henning

Uh, Hae-Won

Uitterlinden, André G

Vaupel, James W

Walston, Jeremy

Westendorp, Rudi GJ

Harris, Tamara B

Lumley, Thomas

van Duijn, Cornelia M

Murabito, Joanne M

United States

2017-06-02T20:05:23Z

2017-06-02T20:05:23Z

2010-05

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.

https://www.ncbi.nlm.nih.gov/pubmed/20304771

glq028

1758-535X

https://hdl.handle.net/10161/14791

eng

Oxford University Press (OUP)

J Gerontol A Biol Sci Med Sci

10.1093/gerona/glq028

Adult

Age 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

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.

Journal article

https://www.ncbi.nlm.nih.gov/pubmed/20304771

478

487

5

Center for Population Health & Aging

Duke

Duke Population Research Institute

Sanford School of Public Policy

Published

65