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

Anne B. Newman, Stefan Walter, Kathryn L. Lunetta, Melissa E. Garcia, P. Eline Slagboom, Kaare Christensen, Alice M. Arnold, Thor Aspelund, Yurii S. Aulchenko, Emelia J. Benjamin, Lene Christiansen, Ralph B. D'Agostino, Annette L. Fitzpatrick, Nora Franceschini, Nicole L. Glazer, Vilmundur Gudnason, Albert Hofman, Robert C. Kaplan, David Karasik, Margaret Kelly-HayesDouglas P. Kiel, Lenore J. Launer, Kristin D. Marciante, Joseph M. Massaro, Iva Miljkovic, Michael A. Nalls, Dena Hernandez, Bruce M. Psaty, Fernando Rivadeneira, Jerome Rotter, Sudha Seshadri, Albert V. Smith, Kent D. Taylor, Henning Tiemeier, Hae Won Uh, André G. Uitterlinden, James W. Vaupel, Jeremy Walston, Rudi G J Westendorp, Tamara B. Harris, Thomas Lumley, Cornelia M. Van Duijn, Joanne M. Murabito

Research output: Contribution to journalArticle

96 Citations (Scopus)

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 × 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.

Original languageEnglish (US)
Pages (from-to)478-487
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume65 A
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Genome-Wide Association Study
Single Nucleotide Polymorphism
Meta-Analysis
Epidemiology
Research
Cohort Studies
Genes
Chromosomes, Human, Pair 10
Alleles
Odds Ratio
Cell Proliferation
Prospective Studies
Phenotype
Health

Keywords

  • Genome-wide association study
  • Longevity
  • Meta-analysis

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

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 C.; 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 G J; Harris, Tamara B.; Lumley, Thomas; Van Duijn, Cornelia M.; Murabito, Joanne M.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 65 A, No. 5, 05.2010, p. 478-487.

Research output: Contribution to journalArticle

Newman, AB, Walter, S, Lunetta, KL, Garcia, ME, Slagboom, PE, Christensen, K, Arnold, AM, Aspelund, T, Aulchenko, YS, Benjamin, EJ, Christiansen, L, D'Agostino, RB, Fitzpatrick, AL, Franceschini, N, Glazer, NL, Gudnason, V, Hofman, A, Kaplan, RC, Karasik, D, Kelly-Hayes, M, Kiel, DP, Launer, LJ, Marciante, KD, Massaro, JM, Miljkovic, I, Nalls, MA, Hernandez, D, Psaty, BM, Rivadeneira, F, Rotter, J, Seshadri, S, Smith, AV, Taylor, KD, Tiemeier, H, Uh, HW, Uitterlinden, AG, Vaupel, JW, Walston, J, Westendorp, RGJ, Harris, TB, Lumley, T, Van Duijn, CM & Murabito, JM 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', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 65 A, no. 5, pp. 478-487. https://doi.org/10.1093/gerona/glq028
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 C. ; 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 G J ; Harris, Tamara B. ; Lumley, Thomas ; Van Duijn, Cornelia M. ; Murabito, Joanne M. / 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. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2010 ; Vol. 65 A, No. 5. pp. 478-487.
@article{ab9ecc5f4d3744a9a5453bb0dcd376e4,
title = "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 × 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.",
keywords = "Genome-wide association study, Longevity, Meta-analysis",
author = "Newman, {Anne B.} and Stefan Walter and Lunetta, {Kathryn L.} and Garcia, {Melissa E.} and Slagboom, {P. Eline} and Kaare Christensen and Arnold, {Alice M.} and Thor Aspelund and Aulchenko, {Yurii S.} and Benjamin, {Emelia J.} and Lene Christiansen and D'Agostino, {Ralph B.} and Fitzpatrick, {Annette L.} and Nora Franceschini and Glazer, {Nicole L.} and Vilmundur Gudnason and Albert Hofman and Kaplan, {Robert C.} and David Karasik and Margaret Kelly-Hayes and Kiel, {Douglas P.} and Launer, {Lenore J.} and Marciante, {Kristin D.} and Massaro, {Joseph M.} and Iva Miljkovic and Nalls, {Michael A.} and Dena Hernandez and Psaty, {Bruce M.} and Fernando Rivadeneira and Jerome Rotter and Sudha Seshadri and Smith, {Albert V.} and Taylor, {Kent D.} and Henning Tiemeier and Uh, {Hae Won} and Uitterlinden, {Andr{\'e} G.} and Vaupel, {James W.} and Jeremy Walston and Westendorp, {Rudi G J} and Harris, {Tamara B.} and Thomas Lumley and {Van Duijn}, {Cornelia M.} and Murabito, {Joanne M.}",
year = "2010",
month = "5",
doi = "10.1093/gerona/glq028",
language = "English (US)",
volume = "65 A",
pages = "478--487",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "5",

}

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 C.

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

Y1 - 2010/5

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

UR - http://www.scopus.com/inward/citedby.url?scp=77951903273&partnerID=8YFLogxK

U2 - 10.1093/gerona/glq028

DO - 10.1093/gerona/glq028

M3 - Article

C2 - 20304771

AN - SCOPUS:77951903273

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

SN - 1079-5006

IS - 5

ER -