Epigenome‐wide analyses identify DNA methylation signatures of dementia risk

Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring

卷:12

Rosie M. Walker¹  Kalyani Pandya¹  Riccardo E. Marioni¹  Mairead L. Bermingham¹  David J. Porteous¹  Kathryn L. Evans¹  Kadi Vaher¹  Stewart W. Morris¹  Konrad Rawlik²  Toni‐Kim Clarke³  Yanni Zeng⁴  Archie Campbell⁵  Andrew M. McIntosh⁶  Andrew D. Bretherick⁷  Caroline Hayward⁷  Carmen Amador⁷ 

[1] Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK;

[2] Division of Genetics and Genomics The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh, Easter Bush, Roslin Edinburgh UK;

[3] Division of Psychiatry University of Edinburgh Royal Edinburgh Hospital Edinburgh UK;

[4] Faculty of Forensic Medicine Zhongshan School of Medicine Sun Yat‐Sen University 74 Zhongshan 2nd Road Guangzhou 510080 China;

[5] Generation Scotland Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK;

[6] MRC Centre for Reproductive Health The Queen's Medical Research Institute Edinburgh Bioquarter 47 Little France Crescent Edinburgh EH16 4TJ UK;

[7] MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK;

关键词: alcohol;    Alzheimer's disease;    dementia;    DNA methylation;    genetic risk score;    risk factors;   

DOI  :  10.1002/dad2.12078

来源: DOAJ

【 摘 要 】

Abstract Introduction Dementia pathogenesis begins years before clinical symptom onset, necessitating the understanding of premorbid risk mechanisms. Here we investigated potential pathogenic mechanisms by assessing DNA methylation associations with dementia risk factors in Alzheimer's disease (AD)–free participants. Methods Associations between dementia risk measures (family history, AD genetic risk score [GRS], and dementia risk scores [combining lifestyle, demographic, and genetic factors]) and whole‐blood DNA methylation were assessed in discovery and replication samples (n = ~400 to ~5000) from Generation Scotland. Results AD genetic risk and two dementia risk scores were associated with differential methylation. The GRS associated predominantly with methylation differences in cis but also identified a genomic region implicated in Parkinson disease. Loci associated with dementia risk scores were enriched for those previously associated with body mass index and alcohol consumption. Discussion Dementia risk measures show widespread association with blood‐based methylation, generating several hypotheses for assessment by future studies.

【 授权许可】

Unknown