Research Paper Volume 16, Issue 8 pp 6694—6716

The association between neighborhood deprivation and DNA methylation in an autopsy cohort

Lindsay Pett1, , Zhenjiang Li2, , Sarina Abrishamcar1, , Kenyaita Hodge2, , Todd Everson1,2, , Grace Christensen1, , Marla Gearing3,4, , Michael S. Kobor5,6,7, , Chaini Konwar5,6, , Julia L. MacIsaac5,6,7, , Kristy Dever5,6,7, , Aliza P. Wingo8,9, , Allan Levey4, , James J. Lah4, , Thomas S. Wingo4,10, , Anke Hüls1,2, ,

  • 1 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
  • 2 Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
  • 3 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
  • 4 Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
  • 5 Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
  • 6 BC Children’s Hospital Research Institute, Vancouver, BC, Canada
  • 7 Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada
  • 8 Division of Mental Health, Atlanta VA Medical Center, Decatur, GA 30033, USA
  • 9 Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322, USA
  • 10 Department of Human Genetics, Emory University, Atlanta, GA 30322, USA

Received: September 1, 2023       Accepted: March 18, 2024       Published: April 24, 2024
How to Cite

Copyright: © 2024 Pett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Previous research has found that living in a disadvantaged neighborhood is associated with poor health outcomes. Living in disadvantaged neighborhoods may alter inflammation and immune response in the body, which could be reflected in epigenetic mechanisms such as DNA methylation (DNAm). We used robust linear regression models to conduct an epigenome-wide association study examining the association between neighborhood deprivation (Area Deprivation Index; ADI), and DNAm in brain tissue from 159 donors enrolled in the Emory Goizueta Alzheimer’s Disease Research Center (Georgia, USA). We found one CpG site (cg26514961, gene PLXNC1) significantly associated with ADI after controlling for covariates and multiple testing (p-value=5.0e-8). Effect modification by APOE ε4 was statistically significant for the top ten CpG sites from the EWAS of ADI, indicating that the observed associations between ADI and DNAm were mainly driven by donors who carried at least one APOE ε4 allele. Four of the top ten CpG sites showed a significant concordance between brain tissue and tissues that are easily accessible in living individuals (blood, buccal cells, saliva), including DNAm in cg26514961 (PLXNC1). Our study identified one CpG site (cg26514961, PLXNC1 gene) that was significantly associated with neighborhood deprivation in brain tissue. PLXNC1 is related to immune response, which may be one biological pathway how neighborhood conditions affect health. The concordance between brain and other tissues for our top CpG sites could make them potential candidates for biomarkers in living individuals.


ABC: Amuloid, Braak, and CERAD; AD: Alzheimer’s disease; ADI: Area Deprivation Index; ADRC: Alzheimer’s Disease Research Center; APOE: Apolipoprotein E; BECon: Blood-Brain Epigenetic Concordance; CERAD: Consortium to Establish a Register for AD; CpG: Cytosine-phosphate-guanine; DNAm: DNA methylation; EWAS: Epigenome-wide association study; GO: Gene ontology; mQTL: Methylation quantitative trait loci; NFTs: Neurofibrillary tangles; RMSE: Root mean square error; SES: Socioeconomic status; SNP: Single nucleotide polymorphism.