A genome-wide association study of aging

Stefan Walter; G Atzmon; EW Demerath; ME Garcia; RC Kaplan; M Kumari; KL Lunetta; Y Milaneschi; T Tanaka; GJ Tranah; U Volker; L Yu; A Arnold; EJ Benjamin; R Biffar; AS Buchman; E Boerwinkle; D Couper; PL De Jager; DA Evans; TB Harris; W Hoffmann; Bert Hofman; D Karasik; DP Kiel; T Kocher; Maris Kuningas; LJ (Lenore) Launer; KK Lohman; PL Lutsey; Johan Mackenbach; K Marciante; BM Psaty; EM Reiman; JI Rotter; S Seshadri; MD Shardell; AV Smith; Cornelia Duijn; J Walston; M.C. Zillikens; S Bandinelli; SE Baumeister; DA Bennett; L Ferrucci; V Gudnason; M Kivimaki; YM Liu; JM Murabito; AB Newman; Henning Tiemeier; N Franceschini

doi:10.1016/j.neurobiolaging.2011.05.026

A genome-wide association study of aging

Stefan Walter, G Atzmon, EW Demerath, ME Garcia, RC Kaplan, M Kumari, KL Lunetta, Y Milaneschi, T Tanaka, GJ Tranah, U Volker, L Yu, A Arnold, EJ Benjamin, R Biffar, AS Buchman, E Boerwinkle, D Couper, PL De Jager, DA EvansTB Harris, W Hoffmann, Bert Hofman, D Karasik, DP Kiel, T Kocher, Maris Kuningas, LJ (Lenore) Launer, KK Lohman, PL Lutsey, Johan Mackenbach, K Marciante, BM Psaty, EM Reiman, JI Rotter, S Seshadri, MD Shardell, AV Smith, Cornelia Duijn, J Walston, M.C. Zillikens, S Bandinelli, SE Baumeister, DA Bennett, L Ferrucci, V Gudnason, M Kivimaki, YM Liu, JM Murabito, AB Newman, Henning Tiemeier, N Franceschini

Research output: Contribution to journal › Article › Academic › peer-review

128 Citations (Scopus)

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 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.

Original language	Undefined/Unknown
Journal	Neurobiology of Aging
Volume	32
Issue number	11
DOIs	https://doi.org/10.1016/j.neurobiolaging.2011.05.026
Publication status	Published - 2011

Research programs

EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC NIHES-02-65-02
EMC NIHES-04-55-01

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.neurobiolaging.2011.05.026

http://hdl.handle.net/1765/33606

Cite this

Walter, S., Atzmon, G., Demerath, EW., Garcia, ME., Kaplan, RC., Kumari, M., Lunetta, KL., Milaneschi, Y., Tanaka, T., Tranah, GJ., Volker, U., Yu, L., Arnold, A., Benjamin, EJ., Biffar, R., Buchman, AS., Boerwinkle, E., Couper, D., De Jager, PL., ... Franceschini, N. (2011). A genome-wide association study of aging. Neurobiology of Aging, 32(11). https://doi.org/10.1016/j.neurobiolaging.2011.05.026

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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 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.",

author = "Stefan Walter and G Atzmon and EW Demerath and ME Garcia and RC Kaplan and M Kumari and KL Lunetta and Y Milaneschi and T Tanaka and GJ Tranah and U Volker and L Yu and A Arnold and EJ Benjamin and R Biffar and AS Buchman and E Boerwinkle and D Couper and {De Jager}, PL and DA Evans and TB Harris and W Hoffmann and Bert Hofman and D Karasik and DP Kiel and T Kocher and Maris Kuningas and Launer, {LJ (Lenore)} and KK Lohman and PL Lutsey and Johan Mackenbach and K Marciante and BM Psaty and EM Reiman and JI Rotter and S Seshadri and MD Shardell and AV Smith and Cornelia Duijn and J Walston and M.C. Zillikens and S Bandinelli and SE Baumeister and DA Bennett and L Ferrucci and V Gudnason and M Kivimaki and YM Liu and JM Murabito and AB Newman and Henning Tiemeier and N Franceschini",

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Walter, S, Atzmon, G, Demerath, EW, Garcia, ME, Kaplan, RC, Kumari, M, Lunetta, KL, Milaneschi, Y, Tanaka, T, Tranah, GJ, Volker, 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, B, 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, Duijn, C, Walston, J, Zillikens, MC, Bandinelli, S, Baumeister, SE, Bennett, DA, Ferrucci, L, Gudnason, V, Kivimaki, M, Liu, YM, Murabito, JM, Newman, AB, Tiemeier, H & Franceschini, N 2011, 'A genome-wide association study of aging', Neurobiology of Aging, vol. 32, no. 11. https://doi.org/10.1016/j.neurobiolaging.2011.05.026

TY - JOUR

T1 - A genome-wide association study of aging

AU - Walter, Stefan

AU - Atzmon, G

AU - Demerath, EW

AU - Garcia, ME

AU - Kaplan, RC

AU - Kumari, M

AU - Lunetta, KL

AU - Milaneschi, Y

AU - Tanaka, T

AU - Tranah, GJ

AU - Volker, U

AU - Yu, L

AU - Arnold, A

AU - Benjamin, EJ

AU - Biffar, R

AU - Buchman, AS

AU - Boerwinkle, E

AU - Couper, D

AU - De Jager, PL

AU - Evans, DA

AU - Harris, TB

AU - Hoffmann, W

AU - Hofman, Bert

AU - Karasik, D

AU - Kiel, DP

AU - Kocher, T

AU - Kuningas, Maris

AU - Launer, LJ (Lenore)

AU - Lohman, KK

AU - Lutsey, PL

AU - Mackenbach, Johan

AU - Marciante, K

AU - Psaty, BM

AU - Reiman, EM

AU - Rotter, JI

AU - Seshadri, S

AU - Shardell, MD

AU - Smith, AV

AU - Duijn, Cornelia

AU - Walston, J

AU - Zillikens, M.C.

AU - Bandinelli, S

AU - Baumeister, SE

AU - Bennett, DA

AU - Ferrucci, L

AU - Gudnason, V

AU - Kivimaki, M

AU - Liu, YM

AU - Murabito, JM

AU - Newman, AB

AU - Tiemeier, Henning

AU - Franceschini, N

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1016/j.neurobiolaging.2011.05.026

DO - 10.1016/j.neurobiolaging.2011.05.026

M3 - Article

C2 - 21782286

SN - 0197-4580

VL - 32

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 11

ER -