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A genome-wide association study of aging |
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| Authors: | Walter Stefan Atzmon Gil Demerath Ellen W Garcia Melissa E Kaplan Robert C Kumari Meena Lunetta Kathryn L Milaneschi Yuri Tanaka Toshiko Tranah Gregory J Völker Uwe Yu Lei Arnold Alice Benjamin Emelia J Biffar Reiner Buchman Aron S Boerwinkle Eric Couper David De Jager Philip L Evans Denis A Harris Tamara B Hoffmann Wolfgang Hofman Albert Karasik David Kiel Douglas P Kocher Thomas Kuningas Maris Launer Lenore J Lohman Kurt K Lutsey Pamela L Mackenbach Johan Marciante Kristin Psaty Bruce M Reiman Eric M Rotter Jerome I Seshadri Sudha Shardell Michelle D Smith Albert V van Duijn Cornelia |
| Affiliation: | a Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands b Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands c Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY, USA d Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA e Department of Genetic, Albert Einstein College of Medicine, Bronx, NY, USA f Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA g Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA h Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA i Department of Epidemiology and Public Health, University College London, London, UK j Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA k Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA l California Pacific Medical Center, San Francisco, CA, USA m Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany n Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA o Department of Biostatistics, University of Washington, Seattle, WA, USA p Sections of General Internal Medicine, Preventive Medicine, Cardiology, and Neurology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA q The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA r Dental School, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany s Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA t Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA u Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA v Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA w Institute of Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany x Center for Integrated Dementia Care Research (CIDC), a scientific cooperation between the Universities and University Hospitals of Rostock and Greifswald, and the German Center for Neurodegenerative Disease (DZNE), Bonn, Germany y Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, MA, USA z Center for Human Genomics, Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA aa Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA bb Group Health Research Unit, Group Health Cooperative, Seattle, WA, USA cc Neurogenomics Division, The Translational Genomics Research Institute, Banner Alzheimer's Institute, Phoenix, AZ, USA dd Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA ee Epidemiology and Public Health, University of Maryland, MD, USA ff Icelandic Heart Association, Kópavogur, Iceland gg Johns Hopkins University School of Medicine, Division of Geriatric Medicine and Gerontology, Baltimore, MD, USA hh Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands ii Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy jj Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA kk Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA ll Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands mm Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA |
| Abstract: | Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10−8). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10−5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity. |
| Keywords: | Genome-wide association analysis Mortality Disease-free survival Longevity Aging Brain aging |
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