TY - JOUR
T1 - A Meta-analysis of four genome-wide association studies of survival to age 90 years or older
T2 - The cohorts for heart and aging research in genomic epidemiology consortium
AU - Newman, Anne B.
AU - Walter, Stefan
AU - Lunetta, Kathryn L.
AU - Garcia, Melissa E.
AU - Slagboom, P. Eline
AU - Christensen, Kaare
AU - Arnold, Alice M.
AU - Aspelund, Thor
AU - Aulchenko, Yurii S.
AU - Benjamin, Emelia J.
AU - Christiansen, Lene
AU - D'Agostino, Ralph B.
AU - Fitzpatrick, Annette L.
AU - Franceschini, Nora
AU - Glazer, Nicole L.
AU - Gudnason, Vilmundur
AU - Hofman, Albert
AU - Kaplan, Robert
AU - Karasik, David
AU - Kelly-Hayes, Margaret
AU - Kiel, Douglas P.
AU - Launer, Lenore J.
AU - Marciante, Kristin D.
AU - Massaro, Joseph M.
AU - Miljkovic, Iva
AU - Nalls, Michael A.
AU - Hernandez, Dena
AU - Psaty, Bruce M.
AU - Rivadeneira, Fernando
AU - Rotter, Jerome
AU - Seshadri, Sudha
AU - Smith, Albert V.
AU - Taylor, Kent D.
AU - Tiemeier, Henning
AU - Uh, Hae Won
AU - Uitterlinden, André G.
AU - Vaupel, James W.
AU - Walston, Jeremy
AU - Westendorp, Rudi G.J.
AU - Harris, Tamara B.
AU - Lumley, Thomas
AU - Van Duijn, Cornelia M.
AU - Murabito, Joanne M.
PY - 2010/5/1
Y1 - 2010/5/1
N2 - 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 × 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 × 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.
AB - 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 × 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 × 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.
KW - Genome-wide association study
KW - Longevity
KW - Meta-analysis
UR - http://www.scopus.com/inward/record.url?scp=77951903273&partnerID=8YFLogxK
U2 - 10.1093/gerona/glq028
DO - 10.1093/gerona/glq028
M3 - Article
C2 - 20304771
AN - SCOPUS:77951903273
SN - 1079-5006
VL - 65 A
SP - 478
EP - 487
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 5
ER -