Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease

Daniel L McCartney; Anna J Stevenson; Rosie M Walker; Jude Gibson; Stewart W Morris; Archie Campbell; Alison D Murray; Heather C Whalley; David J Porteous; Andrew M McIntosh; Kathryn L Evans; Ian J Deary; Riccardo E Marioni

doi:10.1016/j.dadm.2018.05.006

Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease

Daniel L McCartney, Anna J Stevenson, Rosie M Walker, Jude Gibson, Stewart W Morris, Archie Campbell, Alison D Murray, Heather C Whalley, David J Porteous, Andrew M McIntosh, Kathryn L Evans, Ian J Deary, Riccardo E Marioni (Corresponding Author)

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Abstract

Introduction: The "epigenetic clock" is a DNA methylation-based estimate of biological age and is correlated with chronological age-the greatest risk factor for Alzheimer's disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. In this study, we assess the relationship between the epigenetic clock and AD risk factors.

Methods: Multilevel models were used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n = 5100).

Results: We report significant associations between age acceleration and body mass index, total cholesterol to high-density lipoprotein cholesterol ratios, socioeconomic status, high blood pressure, and smoking behavior (Bonferroni-adjusted P < .05).

Discussion: Associations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.

Original language	English
Pages (from-to)	429-437
Number of pages	9
Journal	Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Volume	10
Early online date	21 Jun 2018
DOIs	https://doi.org/10.1016/j.dadm.2018.05.006
Publication status	Published - 2018

Bibliographical note

This work was supported by a Alzheimer's Research UK Major Project grant (ARUK-PG2017B-10). Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team that includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL];104036/Z/14/Z). DNA methylation data collection was funded by the Wellcome Trust Strategic Award (10436/Z/14/Z). The research was conducted in the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports I.J.D. with some additional support from the Dementias Platform UK (MR/L015382/1). A.M.M. and H.C.W. have received support from the Sackler Institute.

Keywords

DNA METHYLATION
Epigenetic clock
Alzheimer's disease
genetics
Generation Scotland

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Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease
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McCartney, D. L., Stevenson, A. J., Walker, R. M., Gibson, J., Morris, S. W., Campbell, A., Murray, A. D., Whalley, H. C., Porteous, D. J., McIntosh, A. M., Evans, K. L., Deary, I. J., & Marioni, R. E. (2018). Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 10, 429-437. https://doi.org/10.1016/j.dadm.2018.05.006

McCartney, DL, Stevenson, AJ, Walker, RM, Gibson, J, Morris, SW, Campbell, A, Murray, AD, Whalley, HC, Porteous, DJ, McIntosh, AM, Evans, KL, Deary, IJ & Marioni, RE 2018, 'Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease', Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, vol. 10, pp. 429-437. https://doi.org/10.1016/j.dadm.2018.05.006

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abstract = "Introduction: The {"}epigenetic clock{"} is a DNA methylation-based estimate of biological age and is correlated with chronological age-the greatest risk factor for Alzheimer's disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. In this study, we assess the relationship between the epigenetic clock and AD risk factors.Methods: Multilevel models were used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n = 5100).Results: We report significant associations between age acceleration and body mass index, total cholesterol to high-density lipoprotein cholesterol ratios, socioeconomic status, high blood pressure, and smoking behavior (Bonferroni-adjusted P < .05).Discussion: Associations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.",

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note = "This work was supported by a Alzheimer's Research UK Major Project grant (ARUK-PG2017B-10). Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team that includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL];104036/Z/14/Z). DNA methylation data collection was funded by the Wellcome Trust Strategic Award (10436/Z/14/Z). The research was conducted in the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports I.J.D. with some additional support from the Dementias Platform UK (MR/L015382/1). A.M.M. and H.C.W. have received support from the Sackler Institute.",

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doi = "10.1016/j.dadm.2018.05.006",

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T1 - Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease

AU - McCartney, Daniel L

AU - Stevenson, Anna J

AU - Walker, Rosie M

AU - Gibson, Jude

AU - Morris, Stewart W

AU - Campbell, Archie

AU - Murray, Alison D

AU - Whalley, Heather C

AU - Porteous, David J

AU - McIntosh, Andrew M

AU - Evans, Kathryn L

AU - Deary, Ian J

AU - Marioni, Riccardo E

N1 - This work was supported by a Alzheimer's Research UK Major Project grant (ARUK-PG2017B-10). Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team that includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL];104036/Z/14/Z). DNA methylation data collection was funded by the Wellcome Trust Strategic Award (10436/Z/14/Z). The research was conducted in the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports I.J.D. with some additional support from the Dementias Platform UK (MR/L015382/1). A.M.M. and H.C.W. have received support from the Sackler Institute.

PY - 2018

Y1 - 2018

N2 - Introduction: The "epigenetic clock" is a DNA methylation-based estimate of biological age and is correlated with chronological age-the greatest risk factor for Alzheimer's disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. In this study, we assess the relationship between the epigenetic clock and AD risk factors.Methods: Multilevel models were used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n = 5100).Results: We report significant associations between age acceleration and body mass index, total cholesterol to high-density lipoprotein cholesterol ratios, socioeconomic status, high blood pressure, and smoking behavior (Bonferroni-adjusted P < .05).Discussion: Associations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.

AB - Introduction: The "epigenetic clock" is a DNA methylation-based estimate of biological age and is correlated with chronological age-the greatest risk factor for Alzheimer's disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. In this study, we assess the relationship between the epigenetic clock and AD risk factors.Methods: Multilevel models were used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n = 5100).Results: We report significant associations between age acceleration and body mass index, total cholesterol to high-density lipoprotein cholesterol ratios, socioeconomic status, high blood pressure, and smoking behavior (Bonferroni-adjusted P < .05).Discussion: Associations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.

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KW - Epigenetic clock

KW - Alzheimer's disease

KW - genetics

KW - Generation Scotland

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DO - 10.1016/j.dadm.2018.05.006

M3 - Article

C2 - 30167451

SN - 2352-8729

VL - 10

SP - 429

EP - 437

JO - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

JF - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

ER -

Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease

Abstract

Bibliographical note

Keywords

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