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      Contributions of neighborhood social environment and air pollution exposure to Black-White disparities in epigenetic aging

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          Abstract

          Racial disparities in many aging-related health outcomes are persistent and pervasive among older Americans, reflecting accelerated biological aging for Black Americans compared to White, known as weathering. Environmental determinants that contribute to weathering are poorly understood. Having a higher biological age, measured by DNA methylation (DNAm), than chronological age is robustly associated with worse age-related outcomes and higher social adversity. We hypothesize that individual socioeconomic status (SES), neighborhood social environment, and air pollution exposures contribute to racial disparities in DNAm aging according to GrimAge and Dunedin Pace of Aging methylation (DPoAm). We perform retrospective cross-sectional analyses among 2,960 non-Hispanic participants (82% White, 18% Black) in the Health and Retirement Study whose 2016 DNAm age is linked to survey responses and geographic data. DNAm aging is defined as the residual after regressing DNAm age on chronological age. We observe Black individuals have significantly accelerated DNAm aging on average compared to White individuals according to GrimAge (239%) and DPoAm (238%). We implement multivariable linear regression models and threefold decomposition to identify exposures that contribute to this disparity. Exposure measures include individual-level SES, census-tract-level socioeconomic deprivation and air pollution (fine particulate matter, nitrogen dioxide, and ozone), and perceived neighborhood social and physical disorder. Race and gender are included as covariates. Regression and decomposition results show that individual-level SES is strongly associated with and accounts for a large portion of the disparity in both GrimAge and DPoAm aging. Higher neighborhood deprivation for Black participants significantly contributes to the disparity in GrimAge aging. Black participants are more vulnerable to fine particulate matter exposure for DPoAm, perhaps due to individual- and neighborhood-level SES, which may contribute to the disparity in DPoAm aging. DNAm aging may play a role in the environment “getting under the skin”, contributing to age-related health disparities between older Black and White Americans.

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          Principal components analysis corrects for stratification in genome-wide association studies.

          Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.
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            The Lancet Commission on pollution and health

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              Neighborhoods and health.

              Features of neighborhoods or residential environments may affect health and contribute to social and race/ethnic inequalities in health. The study of neighborhood health effects has grown exponentially over the past 15 years. This chapter summarizes key work in this area with a particular focus on chronic disease outcomes (specifically obesity and related risk factors) and mental health (specifically depression and depressive symptoms). Empirical work is classified into two main eras: studies that use census proxies and studies that directly measure neighborhood attributes using a variety of approaches. Key conceptual and methodological challenges in studying neighborhood health effects are reviewed. Existing gaps in knowledge and promising new directions in the field are highlighted.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 July 2023
                2023
                : 18
                : 7
                : e0287112
                Affiliations
                [1 ] Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [2 ] Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [3 ] Division of Geriatric Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [4 ] Geriatrics and Extended Care, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America
                [5 ] Center for Health Equity Research and Promotion, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America
                [6 ] Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                Graduate Institute of Biomedical Sciences, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-2798-1411
                https://orcid.org/0000-0003-3994-4343
                https://orcid.org/0000-0002-7581-6405
                Article
                PONE-D-22-27535
                10.1371/journal.pone.0287112
                10321643
                37405974
                94c49130-bef5-44c6-9da3-6a3a1e8e5f52
                © 2023 Yannatos et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 October 2022
                : 29 May 2023
                Page count
                Figures: 3, Tables: 4, Pages: 22
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: R01-AG066152
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: R01- AG070885
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: P30-AG072979
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100004897, Pennsylvania Department of Health;
                Award ID: 2019NF4100087335
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100016954, Institute on Aging, University of Pennsylvania;
                Award Recipient :
                This work was supported by National Institute on Aging: R01-AG066152 (CM), R01- AG070885 (RB), P30-AG072979 (CM). Additional support includes Pennsylvania Department of Health (2019NF4100087335; CM), and Penn Institute on Aging (CM). National Institute on Aging: https://www.nia.nih.gov Pennsylvania Department of Health: https://www.health.pa.gov/Pages/default.aspx Penn Institute on Aging: https://www.med.upenn.edu/aging/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Earth Sciences
                Geography
                Human Geography
                Social Geography
                Neighborhoods
                Social Sciences
                Human Geography
                Social Geography
                Neighborhoods
                Medicine and Health Sciences
                Health Care
                Socioeconomic Aspects of Health
                Medicine and Health Sciences
                Public and Occupational Health
                Socioeconomic Aspects of Health
                Biology and Life Sciences
                Developmental Biology
                Organism Development
                Aging
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Aging
                Ecology and Environmental Sciences
                Pollution
                Air Pollution
                Medicine and Health Sciences
                Public and Occupational Health
                Behavioral and Social Aspects of Health
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Biology and life sciences
                Cell biology
                Chromosome biology
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                Epigenetics
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                Gene expression
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                DNA
                DNA modification
                DNA methylation
                Biology and life sciences
                Biochemistry
                Nucleic acids
                DNA
                DNA modification
                DNA methylation
                Biology and life sciences
                Genetics
                Epigenetics
                DNA modification
                DNA methylation
                Biology and life sciences
                Genetics
                Gene expression
                DNA modification
                DNA methylation
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Custom metadata
                Data Availability: Data used in this study are available through a third-party, the Health and Retirement Study. However, once a researcher has obtained access to the data, they can use our code available at github.com/pennbindlab to recreate the minimal data set. Description of the data set and source: The Health and Retirement Study (HRS) is sponsored by the National Institute on Aging (grant number NIA U01 AG009740) and is conducted by the University of Michigan. It is a longitudinal panel survey study that collects in-depth survey interviews and biological samples from a representative sample of Americans 50 and older. Study participants’ geographic location and Contextual Data Resource data are available only under special agreement because they contain sensitive and/or confidential information. Verification of permission to use the data set: Restricted Data Agreement # 2021-084 was approved on October 15, 2021. Information to apply to gain access: Researchers must apply for access through HRS at the site https://hrs.isr.umich.edu/data-products/restricted-data. The application and use of data are free of charge. IRB approval is required. All questions related to HRS Restricted data should be sent to hrsrdaapplication@ 123456umich.edu .

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