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
Year: 2010
Type: review
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.
Authors: 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 Kaplan, David Karasik, Margaret Kelly-Hayes, Douglas 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
Institutions: University of Pittsburgh, Erasmus MC, Rotterdam Study, Boston University, National Heart, Lung, and Blood Institute, Framingham Heart Study, National Institutes of Health, National Institute on Aging, Leiden University Medical Center, Netherlands Consortium for Healthy Ageing, University of Southern Denmark, University of Washington, University of Iceland, University of North Carolina at Chapel Hill, Icelandic Heart Association, Albert Einstein College of Medicine, Harvard University, Hebrew SeniorLife, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute, Cedars-Sinai Medical Center, Erasmus MC - Sophia Children’s Hospital, Duke University, Johns Hopkins University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Institute for Clinical and Translational Research (UL1), Exceptional Aging Across the Life Span: Framingham Study, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, Oldest-old Mortality - Demographic Models and Analysis, Neurotrophic Factors: Genetic Variation and Serum Levels in Brain Aging, Epidemiology and Genetics of Skeletal Muscle Composition, Aging and Inflammation: Longitudinal Markers and Genetics in the Framingham Study, CHS Events Follow-up Study, General Clinical Research Center, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), AD Gene Discovery: Exome Chip, New Endophenotypes & Functional Studies in CHARGE, Pittsburgh Older Americans Independence Center, Novel Molecular Biomarkers of Bone Microarchitecture, Diabetes Research Center (DRC), Longevity Consortium
OpenAlex ID: W2118729796