Journal
NEUROBIOLOGY OF AGING
Volume 32, Issue 11, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.05.026
Keywords
Genome-wide association analysis; Mortality; Disease-free survival; Longevity; Aging; Brain aging
Categories
Funding
- Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]
- Netherlands Organisation for Scientific Research (NWO) [904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419, 175.010. 2005.011, 911-03-012, 017.106.370]
- Netspar-Living longer for a good health
- Erasmus Medical Center
- Erasmus University in Rotterdam
- Netherlands Organization for Health Research and Development
- Netherlands Research Institute for Diseases in the Elderly
- Dutch Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission
- Municipality of Rotterdam, the Netherlands
- National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652, N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]
- National Institute of Aging [R01 AG031890, R01AG029451, R01 AR/AG 41398, N01AG62101, N01AG62103, N01AG62106, 1R03AG032498-01, 1R01AG032098-01A1]
- National Institute of Neurological Disorders and Stroke
- National Center for Research Resources [M01-RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- Affymetrix, Inc., [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
- Boston Medical Center
- National Institute of Arthritis, Musculoskeletal and Skin Diseases
- NIH [N01-AG-12100, HHSN268200782096C]
- Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- Italian Ministry of Health [ICS110.1/RF97.71]
- U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]
- NIH, National Institute on Aging
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg, West Pomerania
- [AG033193]
- [AG081220]
- [NS17950]
- [P30AG013846]
- [1R01-AG028321]
- MRC [G0902037] Funding Source: UKRI
- British Heart Foundation [RG/07/008/23674] Funding Source: researchfish
- Medical Research Council [G19/35, G0100222, G8802774, G0902037] Funding Source: researchfish
Ask authors/readers for more resources
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 x 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. (C) 2011 Elsevier Inc. All rights reserved.
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