Title | A genome-wide association study of aging. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Walter, S, Atzmon, G, Demerath, EW, Garcia, ME, Kaplan, RC, Kumari, M, Lunetta, KL, Milaneschi, Y, Tanaka, T, Tranah, GJ, Völker, U, Yu, L, Arnold, A, Benjamin, EJ, Biffar, R, Buchman, AS, Boerwinkle, E, Couper, D, De Jager, PL, Evans, DA, Harris, TB, Hoffmann, W, Hofman, A, Karasik, D, Kiel, DP, Kocher, T, Kuningas, M, Launer, LJ, Lohman, KK, Lutsey, PL, Mackenbach, J, Marciante, K, Psaty, BM, Reiman, EM, Rotter, JI, Seshadri, S, Shardell, MD, Smith, AV, van Duijn, C, Walston, J, Zillikens, CM, Bandinelli, S, Baumeister, SE, Bennett, DA, Ferrucci, L, Gudnason, V, Kivimaki, M, Liu, Y, Murabito, JM, Newman, AB, Tiemeier, H, Franceschini, N |
Journal | Neurobiol Aging |
Volume | 32 |
Issue | 11 |
Pagination | 2109.e15-28 |
Date Published | 2011 Nov |
ISSN | 1558-1497 |
Keywords | Aging, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Longevity |
Abstract | <p>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.</p> |
DOI | 10.1016/j.neurobiolaging.2011.05.026 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 21782286 |
PubMed Central ID | PMC3193030 |
Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States 1R03AG032498-01 / AG / NIA NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States M01 RR00425 / RR / NCRR NIH HHS / United States UL1 TR000005 / TR / NCATS NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States R01 HL036310 / HL / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States G19/35 / / Medical Research Council / United Kingdom N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U19 AG023122 / AG / NIA NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States G0100222 / / Medical Research Council / United Kingdom R01 MD009164 / MD / NIMHD NIH HHS / United States R01 AG030146 / AG / NIA NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States 1R01-AG028321 / AG / NIA NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States G8802774 / / Medical Research Council / United Kingdom R01 AG017917 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States G0902037 / / Medical Research Council / United Kingdom R01 HL087652 / HL / NHLBI NIH HHS / United States R01 AR/AG 41398 / AG / NIA NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States R01 AR041398 / AR / NIAMS NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States R37 AG013196 / AG / NIA NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States / / Intramural NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States P30AG013846 / AG / NIA NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States R01 AG029451 / AG / NIA NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States R03 AG032498 / AG / NIA NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States AG081220 / AG / NIA NIH HHS / United States R01 AG013196 / AG / NIA NIH HHS / United States R01AG029451 / AG / NIA NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States P30 AG019610 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 AG028321 / AG / NIA NIH HHS / United States 263 MD 9164 / MD / NIMHD NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 AG031890 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States RG/07/008/23674 / / British Heart Foundation / United Kingdom |