Use of Correct and Incorrect Methods of Accounting for Age in Studies of Epigenetic Accelerated Aging: Implications and Recommendations for Best Practices.

Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation (DNAm) patterns), we report on 3 different approaches in the epidemiologic literature-1 incorrect and 2 correct-on the treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%) or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introduced by use of the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias towards the null, and we discuss implications for extant research and recommendations for best practices.

Tabby2: a user-friendly web tool for forecasting state-level TB outcomes in the United States.

BACKGROUND: In the United States, the tuberculosis (TB) disease burden and associated factors vary substantially across states. While public health agencies must choose how to deploy resources to combat TB and latent tuberculosis infection (LTBI), state-level modeling analyses to inform policy decisions have not been widely available. METHODS: We developed a mathematical model of TB epidemiology linked to a web-based user interface - Tabby2. The model is calibrated to epidemiological and demographic data for the United States, each U.S. state, and the District of Columbia. Users can simulate pre-defined scenarios describing approaches to TB prevention and treatment or create their own intervention scenarios. Location-specific results for epidemiological outcomes, service utilization, costs, and cost-effectiveness are reported as downloadable tables and customizable visualizations. To demonstrate the tool's functionality, we projected trends in TB outcomes without additional intervention for all 50 states and the District of Columbia. We further undertook a case study of expanded treatment of LTBI among non-U.S.-born individuals in Massachusetts, covering 10% of the target population annually over 2025-2029. RESULTS: Between 2022 and 2050, TB incidence rates were projected to decline in all states and the District of Columbia. Incidence projections for the year 2050 ranged from 0.03 to 3.8 cases (median 0.95) per 100,000 persons. By 2050, we project that majority (> 50%) of TB will be diagnosed among non-U.S.-born persons in 46 states and the District of Columbia; per state percentages range from 17.4% to 96.7% (median 83.0%). In Massachusetts, expanded testing and treatment for LTBI in this population was projected to reduce cumulative TB cases between 2025 and 2050 by 6.3% and TB-related deaths by 8.4%, relative to base case projections. This intervention had an incremental cost-effectiveness ratio of $180,951 (2020 USD) per quality-adjusted life year gained from the societal perspective. CONCLUSIONS: Tabby2 allows users to estimate the costs, impact, and cost-effectiveness of different TB prevention approaches for multiple geographic areas in the United States. Expanded testing and treatment for LTBI could accelerate declines in TB incidence in the United States, as demonstrated in the Massachusetts case study.

Decreasing Survey Response Rates in the Time of COVID-19: Implications for Analyses of Population Health and Health Inequities.

Objectives. To examine whether, and if so how, US national and state survey response rates changed after the onset of the COVID-19 pandemic. Methods. We compared the change in response rates between 2020 and 2019 of 6 (3 social and economic, 3 health focused) major US national surveys (2 with state response rates). Results. All the ongoing surveys except 1 reported relative decreases (∼29%) in response rates. For example, the household response rate to the US Census American Community Survey decreased from 86.0% in 2019 to 71.2% in 2020, and the response rate of the US National Health Interview Survey decreased from 60.0% to 42.7% from the first to the second quarter of 2020. For all surveys, the greatest decreases in response rates occurred among persons with lower income and lower education. Conclusions. Socially patterned decreases in response rates pose serious challenges and must be addressed explicitly in all studies relying on data obtained since the onset of the pandemic. Public Health Implications. Artifactual reduction of estimates of the magnitude of health inequities attributable to differential response rates could adversely affect efforts to reduce these inequities. (Am J Public Health. 2023;113(6):667-670. https://doi.org/10.2105/AJPH.2023.307267).

Contextualizing Response Rates During the COVID-19 Pandemic: Experiences From a Boston-Based Community Health Centers Study.

OBJECTIVES: The focus of this study was to calculate and contextualize response rates for a community-based study conducted during the COVID-19 pandemic, a topic on which scant data exist, and to share lessons learned from recruiting and enrolling for implementation of future studies. DESIGN: The Life+Health Study, a cross-sectional population-based study designed to advance novel methods to measure and analyze multiple forms of discrimination for population health research. SETTING: The study recruited participants from 3 community health centers in Boston, Massachusetts, between May 2020 and July 2022. PARTICIPANTS: A total of 699 adult participants between the ages of 25 and 64 years who were born in the United States and had visited one of the health centers within the last 2 years. MAIN OUTCOME MEASURES: The response rate was calculated as follows: (number of completions + number of dropouts)/(dropouts + enrollments). To contextualize this response rate, we synthesized evidence pertaining to local COVID-19 case counts, sociopolitical events, pandemic-related restrictions and project protocol adjustments, and examples of interactions with patients. RESULTS: Our study had a lower-than-expected response rate (48.4%), with the lowest rates from the community health centers serving primarily low-income patients of color. Completion rates were lower during periods of higher COVID-19 case counts. We describe contextual factors that led to challenges and lessons learned from recruiting during the pandemic, including the impact of US sociopolitical events. CONCLUSIONS: The Life+Health Study concluded recruitment during the pandemic with a lower-than-expected response rate, as also reported in 4 other US publications focused on the impact of COVID-19 on response rates in community-based studies. Our results provide an example of the impact of the pandemic and related US sociopolitical events on response rates that can serve as a framework for contextualizing other research conducted during the pandemic and highlight the importance of best practices in research recruitment with underserved populations.

Time Since Infection and Risks of Future Disease for Individuals with Mycobacterium tuberculosis Infection in the United States.

BACKGROUND: Risk of tuberculosis (TB) declines over time since Mycobacterium tuberculosis infection, but progression to clinical disease is still possible decades later. In the United States, most TB cases result from the progression of latent TB infection acquired over 2 years ago. METHODS: We synthesized evidence on TB natural history and incidence trends using a transmission-dynamic model. For the 2020 US population, we estimated average time since infection and annual, cumulative, and remaining lifetime risks of progression to TB, by nativity and age. RESULTS: For a newly infected adult with no other risk factors for progression to TB, estimated rates of progression declined from 38 (95% uncertainty interval: 33, 46) to 0.38 (0.32, 0.45) per 1000 person-years between the first and 25th year since infection. Cumulative risk over 25 years from new infection was 7.9% (7.0, 8.9). In 2020, an estimated average age of individuals with prevalent infection was 62 (61, 63) for the US-born population, 55 (54, 55) for non-US-born, and 57 (56, 58) overall. Average risks of developing TB over the remaining lifetime were 1.2% (1.0, 1.4) for US-born, 2.2% (1.8, 2.6) for non-US-born, and 1.9% (1.6, 2.2) for the general population. Risk estimates were higher for younger age groups. CONCLUSIONS: Our analysis suggests that, although newly infected individuals face appreciable lifetime TB risks, most US individuals with latent TB infection were infected long ago, and face low future risks of developing TB. Better approaches are needed for identifying recently infected individuals and those with elevated progression risks.

Modeling the Cost-Effectiveness of Express Multisite Gonorrhea Screening Among Men Who Have Sex With Men in the United States.

BACKGROUND: Men who have sex with men (MSM) experience high rates of gonococcal infection at extragenital (rectal and pharyngeal) anatomic sites, which often are missed without asymptomatic screening and may be important for onward transmission. Implementing an express pathway for asymptomatic MSM seeking routine screening at their clinic may be a cost-effective way to improve extragenital screening by allowing patients to be screened at more anatomic sites through a streamlined, less costly process. METHODS: We modified an agent-based model of anatomic site-specific gonococcal infection in US MSM to assess the cost-effectiveness of an express screening pathway in which all asymptomatic MSM presenting at their clinic were screened at the urogenital, rectal, and pharyngeal sites but forewent a provider consultation and physical examination and self-collected their own samples. We calculated the cumulative health effects expressed as gonococcal infections and cases averted over 5 years, labor and material costs, and incremental cost-effectiveness ratios for express versus traditional scenarios. RESULTS: The express scenario averted more infections and cases in each intervention year. The increased diagnostic costs of triple-site screening were largely offset by the lowered visit costs of the express pathway and, from the end of year 3 onward, this pathway generated small cost savings. However, in a sensitivity analysis of assumed overhead costs, cost savings under the express scenario disappeared in the majority of simulations once overhead costs exceeded 7% of total annual costs. CONCLUSIONS: Express screening may be a cost-effective option for improving multisite anatomic screening among US MSM.

Impact of Effective Global Tuberculosis Control on Health and Economic Outcomes in the United States.

Rationale: Most U.S. residents who develop tuberculosis (TB) were born abroad, and U.S. TB incidence is increasingly driven by infection risks in other countries.Objectives: To estimate the potential impact of effective global TB control on health and economic outcomes in the United States.Methods: We estimated outcomes using linked mathematical models of TB epidemiology in the United States and migrants' birth countries. A base-case scenario extrapolated country-specific TB incidence trends. We compared this with scenarios in which countries achieve 90% TB incidence reductions between 2015 and 2035, as targeted by the World Health Organization's End TB Strategy ("effective global TB control"). We also considered pessimistic scenarios of flat TB incidence trends in individual countries.Measurements and Main Results: We estimated TB cases, deaths, and costs and the total economic burden of TB in the United States. Compared with the base-case scenario, effective global TB control would avert 40,000 (95% uncertainty interval, 29,000-55,000) TB cases in the United States in 2020-2035. TB incidence rates in 2035 would be 43% (95% uncertainty interval, 34-54%) lower than in the base-case scenario, and 49% (95% uncertainty interval, 44-55%) lower than in 2020. Summed over 2020-2035, this represents 0.8 billion dollars (95% uncertainty interval, 0.6-1.0 billion dollars) in averted healthcare costs and $2.5 billion dollars (95% uncertainty interval, 1.7-3.6 billion dollars) in productivity gains. The total U.S. economic burden of TB (including the value of averted TB deaths) would be 21% (95% uncertainty interval, 16-28%) lower (18 billion dollars [95% uncertainty level, 8-32 billion dollars]).Conclusions: In addition to producing major health benefits for high-burden countries, strengthened efforts to achieve effective global TB control could produce substantial health and economic benefits for the United States.

The target/perpetrator brief-implicit association test (B-IAT): an implicit instrument for efficiently measuring discrimination based on race/ethnicity, sex, gender identity, sexual orientation, weight, and age.

BACKGROUND: To date, research assessing discrimination has employed primarily explicit measures (i.e., self-reports), which can be subject to intentional and social desirability processes. Only a few studies, focusing on sex and race/ethnicity discrimination, have relied on implicit measures (i.e., Implicit Association Test, IAT), which permit assessing mental representations that are outside of conscious control. This study aims to advance measurement of discrimination by extending the application of implicit measures to multiple types of discrimination and optimizing the time required for the administration of these instruments. METHODS: Between September 27th 2019 and February 9th 2020, we conducted six experiments (984 participants) to assess implicit and explicit discrimination based on race/ethnicity, sex, gender identity, sexual orientation, weight, and age. Implicit discrimination was measured by using the Brief-Implicit Association Test (B-IAT), a new validated version of the IAT developed to shorten the time needed (from ≈15 to ≈2 min) to assess implicit mental representations, while explicit discrimination was assessed using self-reported items. RESULTS: Among participants (mean age = 37.8), 68.6% were White Non-Hispanic; 69% were females; 76.1% were heterosexual; 90.7% were gender conforming; 52.8% were medium weight; and 41.5% had an advanced level of education. Overall, we found implicit and explicit recognition of discrimination towards all the target groups (stronger for members of the target than dominant groups). Some exceptions emerged in experiments investigating race/ethnicity and weight discrimination. In the racism experiment, only people of Color showed an implicit recognition of discrimination towards the target group, while White people were neutral. In the fatphobia experiment, participants who were not heavy showed a slight implicit recognition of discrimination towards the dominant group, while heavy participants were neutral. CONCLUSIONS: This study provides evidence that the B-IAT is a valuable tool for quickly assessing multiple types of implicit discrimination. It shows also that implicit and explicit measures can display diverging results, thus indicating that research would benefit from the use of both these instruments. These results have important implications for the assessment of discrimination in health research as well as in social and psychological science.

Exploring How Epidemic Context Influences Syphilis Screening Impact: A Mathematical Modeling Study.

BACKGROUND: The current syphilis epidemic in the United States is concentrated in gay, bisexual, and other men who have sex with men (MSM), but substantial heterosexual transmission is reported in some parts of the country. Using the US states of Louisiana and Massachusetts as case studies, we investigated how epidemic context influences the impact of population screening approaches for syphilis control. METHODS: We constructed a compartmental metapopulation model parameterized to describe observed patterns of syphilis transmission. We estimated the impact of different approaches to screening, including perfect adherence to current US screening guidelines in MSM. RESULTS: In Louisiana, where syphilis cases are more evenly distributed among MSM and heterosexual populations, we projected that screening according to guidelines would contribute to no change or an increase in syphilis burden, compared with burden with current estimated screening coverage. In Massachusetts, which has a more MSM-focused outbreak, we projected that screening according to guidelines would be as or more effective than current screening coverage in most population groups. CONCLUSIONS: Men who have sex with men-focused approaches to screening may be insufficient for control when there is substantial transmission in heterosexual populations. Epidemic characteristics may be useful when identifying at-risk groups for syphilis screening.

Population-level Benefits of Extragenital Gonorrhea Screening Among Men Who Have Sex With Men: An Exploratory Modeling Analysis.

BACKGROUND: Men who have sex with men (MSM) are disproportionately burdened by gonorrhea and face high rates of extragenital (rectal and pharyngeal) infection, which is mostly asymptomatic and often missed by urogenital-only screening. Extragenital screening likely remains below Centers for Disease Control and Prevention-recommended levels. Because increasing screening coverage is often resource-intensive, we assessed whether improved extragenital screening among men already presenting at clinics could lead to substantial reductions in prevalence and incidence. METHODS: We calibrated an agent-based model of site- and race-specific gonorrhea infection in MSM to explicitly model multisite infection within an individual and transmission via anal, orogenital, and ororectal sex. Compared with current screening levels, we assessed the impact of increasing screening at (1) both extragenital sites, (2) only the rectal site, and (3) only the pharyngeal site among men already being urogenitally screened. RESULTS: All scenarios reduced prevalence and incidence, with improved screening at both extragenital sites having the largest effect across outcomes. Extragenitally screening 100% of men being urogenitally screened reduced site-specific prevalence by an average of 42% (black MSM) and 50% (white MSM), with these values dropping by approximately 10% and 20% for each race group when targeting only the rectum and only the pharynx, respectively. However, increasing only rectal screening was more efficient in terms of the number of screens needed to avert an infection as this avoided duplicative screens due to rectum/pharynx multisite infection. CONCLUSIONS: Improved extragenital screening substantially reduced site-specific gonorrhea prevalence and incidence, with strategies aimed at increasing rectal screening proving the most efficient.

The Potential Population-Level Impact of Different Gonorrhea Screening Strategies in Baltimore and San Francisco: An Exploratory Mathematical Modeling Analysis.

BACKGROUND: Baltimore and San Francisco represent high burden areas for gonorrhea in the United States. We explored different gonorrhea screening strategies and their comparative impact in the 2 cities. METHODS: We used a compartmental transmission model of gonorrhea stratified by sex, sexual orientation, age, and race/ethnicity, calibrated to city-level surveillance data for 2010 to 2017. We analyzed the benefits of 5-year interventions which improved retention in care cascade or increased screening from current levels. We also examined a 1-year outreach screening intervention of high-activity populations. RESULTS: In Baltimore, annual screening of population aged 15 to 24 years was the most efficient of the 5-year interventions with 17.9 additional screening tests (95% credible interval [CrI], 11.8-31.4) needed per infection averted while twice annual screening of the same population averted the most infections (5.4%; 95% CrI, 3.1-8.2%) overall with 25.3 (95% CrI, 19.4-33.4) tests per infection averted. In San Francisco, quarter-annual screening of all men who have sex with men was the most efficient with 16.2 additional (95% CrI, 12.5-44.5) tests needed per infection averted, and it also averted the most infections (10.8%; 95% CrI, 1.2-17.8%). Interventions that reduce loss to follow-up after diagnosis improved outcomes. Depending on the ability of a short-term outreach screening to screen populations at higher acquisition risk, such interventions can offer efficient ways to expand screening coverage. CONCLUSIONS: Data on gonorrhea prevalence distribution and time trends locally would improve the analyses. More focused intervention strategies could increase the impact and efficiency of screening interventions.

COVID-19: US federal accountability for entry, spread, and inequities-lessons for the future.

The United States (US) has been among those nations most severely affected by the first-and subsequent-phases of the pandemic of COVID-19, the disease caused by SARS-CoV-2. With only 4% of the worldwide population, the US has seen about 22% of COVID-19 deaths. Despite formidable advantages in resources and expertise, presently the per capita mortality rate is over 585/million, respectively 2.4 and 5 times higher compared to Canada and Germany. As we enter Fall 2020, the US is enduring ongoing outbreaks across large regions of the country. Moreover, within the US, an early and persistent feature of the pandemic has been the disproportionate impact on populations already made vulnerable by racism and dangerous jobs, inadequate wages, and unaffordable housing, and this is true for both the headline public health threat and the additional disastrous economic impacts. In this article we assess the impact of missteps by the Federal Government in three specific areas: the introduction of the virus to the US and the establishment of community transmission; the lack of national COVID-19 workplace standards and enforcement, and lack of personal protective equipment (PPE) for workplaces as represented by complaints to the Occupational Safety and Health Administration (OSHA) which we find are correlated with deaths 16 days later (ρ = 0.83); and the total excess deaths in 2020 to date already total more than 230,000, while COVID-19 mortality rates exhibit severe-and rising-inequities in race/ethnicity, including among working age adults.

Epigenetic Aging and Racialized, Economic, and Environmental Injustice: NIMHD Social Epigenomics Program.

Importance: Epigenetic age acceleration is associated with exposure to social and economic adversity and may increase the risk of premature morbidity and mortality. However, no studies have included measures of structural racism, and few have compared estimates within or across the first and second generation of epigenetic clocks. Objective: To determine whether epigenetic age acceleration is positively associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods. Design, Setting, and Participants: This cross-sectional study used data from the My Body My Story (MBMS) study between August 8, 2008, and December 31, 2010, and examination 5 of the Multi-Ethnic Atherosclerosis Study (MESA) from April 1, 2010, to February 29, 2012. In the MBMS, DNA extraction was performed in 2021; linkage of structural measures to the MBMS and MESA, in 2022. US-born individuals were randomly selected from 4 community health centers in Boston, Massachusetts (MBMS), and 4 field sites in Baltimore, Maryland; Forsyth County, North Carolina; New York City, New York; and St Paul, Minnesota (MESA). Data were analyzed from November 13, 2021, to August 31, 2023. Main Outcomes and Measures: Ten epigenetic clocks (6 first-generation and 4 second-generation), computed using DNA methylation data (DNAm) from blood spots (MBMS) and purified monocytes (MESA). Results: The US-born study population included 293 MBMS participants (109 men [37.2%], 184 women [62.8%]; mean [SD] age, 49.0 [8.0] years) with 224 Black non-Hispanic and 69 White non-Hispanic participants and 975 MESA participants (492 men [50.5%], 483 women [49.5%]; mean [SD] age, 70.0 [9.3] years) with 229 Black non-Hispanic, 191 Hispanic, and 555 White non-Hispanic participants. Of these, 140 (11.0%) exhibited accelerated aging for all 5 clocks whose estimates are interpretable on the age (years) scale. Among Black non-Hispanic MBMS participants, epigenetic age acceleration was associated with being born in a Jim Crow state by 0.14 (95% CI, 0.003-0.27) SDs and with birth state conservatism by 0.06 (95% CI, 0.01-0.12) SDs, pooling across all clocks. Low parental educational level was associated with epigenetic age acceleration, pooling across all clocks, for both Black non-Hispanic (0.24 [95% CI, 0.08-0.39] SDs) and White non-Hispanic (0.27 [95% CI, 0.03-0.51] SDs) MBMS participants. Adult impoverishment was positively associated with the pooled second-generation clocks among the MESA participants (Black non-Hispanic, 0.06 [95% CI, 0.01-0.12] SDs; Hispanic, 0.07 [95% CI, 0.01-0.14] SDs; White non-Hispanic, 0.05 [95% CI, 0.01-0.08] SDs). Conclusions and Relevance: The findings of this cross-sectional study of MBMS and MESA participants suggest that epigenetic age acceleration was associated with racialized and economic injustice, potentially contributing to well-documented inequities in premature mortality. Future research should test the hypothesis that epigenetic accelerated aging may be one of the biological mechanisms underlying the well-documented elevated risk of premature morbidity and mortality among social groups subjected to racialized and economic injustice.

Addressing spatial misalignment in population health research: a case study of US congressional district political metrics and county health data.

Areal spatial misalignment, which occurs when data on multiple variables are collected using mismatched boundary definitions, is a ubiquitous obstacle to data analysis in public health and social science research. As one example, the emerging sub-field studying the links between political context and health in the United States faces significant spatial misalignment-related challenges, as the congressional districts (CDs) over which political metrics are measured and administrative units, e.g., counties, for which health data are typically released, have a complex misalignment structure. Standard population-weighted data realignment procedures can induce measurement error and invalidate inference, which has prompted the development of fully model-based approaches for analyzing spatially misaligned data. One such approach, atom-based regression models (ABRM), holds particular promise but has scarcely been used in practice due to the lack of appropriate software or examples of implementation. ABRM use "atoms", the areas created by intersecting all sets of units on which variables of interest are measured, as the units of analysis and build models for the atom-level data, treating the atom-level variables (generally unmeasured) as latent variables. In this paper, we demonstrate the feasibility and strengths of the ABRM in a case study of the association between political representatives' voting behavior (CD-level) and COVID-19 mortality rates (county-level) in a post-vaccine period. The adjusted ABRM results suggest that more conservative voting record is associated with an increase in COVID-19 mortality rates, with estimated associations smaller in magnitude but consistent in direction with those of standard realignment methods. The results also indicate that ABRM may enable more robust confounding adjustment and more realistic uncertainty estimates, properly representing the uncertainties arising from all analytic procedures. We also implement the ABRM in modern optimized Bayesian computing programs and make our code publicly available, which may enable these methods to be more widely adopted.

Using Implicit Measures of Discrimination: White, Black, and Hispanic Participants Respond Differently to Group-Specific Racial/Ethnic Categories vs. the General Category "People of Color" in the USA.

Recent studies showed that implicit measures are valuable instruments for assessing exposure to discrimination and predicting negative physical conditions. Between March 10, 2020, and April 1, 2020, we conducted three experiments (577 participants) in the USA to evaluate the use of group-specific vs. general race/ethnicity categories in implicit measures of discrimination. We measured implicit discrimination and attitudes towards the general race/ethnicity category "people of color" (POC) and two specific race/ethnicity categories (i.e., "Black people" and "Hispanic people"). Implicit discrimination and attitudes were assessed using the Brief Implicit Association Test (B-IAT). Among participants (mean age = 37, standard deviation = 10.5), 50% identified as White non-Hispanic (NH), 33.3% as Black NH, and 16.7% as Hispanic; 71.7% were female and 72.2% had a bachelor's degree or higher. We found an implicit discrimination towards target groups and an in-group preference among all participant groups only when specific race/ethnicity categories were used in the B-IAT. When the general category POC was used, we observed a discrimination towards POC only for Black NH participants, while White NH participants showed no discrimination. Similarly, Black NH participants showed no in-group preference for POC, but did show an in-group preference for Black people. These results suggest that using the category POC in implicit measures may be inappropriate when evaluating discrimination and attitudes towards Black and Hispanic individuals as it may not capture specific experiences of discrimination and identity in these groups.

Epigenetic clocks and research implications of the lack of data on whom they have been developed: a review of reported and missing sociodemographic characteristics.

Epigenetic clocks are increasingly being used as a tool to assess the impact of a wide variety of phenotypes and exposures on healthy ageing, with a recent focus on social determinants of health. However, little attention has been paid to the sociodemographic characteristics of participants on whom these clocks have been based. Participant characteristics are important because sociodemographic and socioeconomic factors are known to be associated with both DNA methylation variation and healthy ageing. It is also well known that machine learning algorithms have the potential to exacerbate health inequities through the use of unrepresentative samples - prediction models may underperform in social groups that were poorly represented in the training data used to construct the model. To address this gap in the literature, we conducted a review of the sociodemographic characteristics of the participants whose data were used to construct 13 commonly used epigenetic clocks. We found that although some of the epigenetic clocks were created utilizing data provided by individuals from different ages, sexes/genders, and racialized groups, sociodemographic characteristics are generally poorly reported. Reported information is limited by inadequate conceptualization of the social dimensions and exposure implications of gender and racialized inequality, and socioeconomic data are infrequently reported. It is important for future work to ensure clear reporting of tangible data on the sociodemographic and socioeconomic characteristics of all the participants in the study to ensure that other researchers can make informed judgements about the appropriateness of the model for their study population.

Epigenetic aging & embodying injustice: US My Body My Story and Multi-Ethnic Atherosclerosis Study.

Importance: Epigenetic accelerated aging is associated with exposure to social and economic adversity and may increase risk of premature morbidity and mortality. However, no studies have included measures of structural racism and few have compared estimates within or across the 1st and 2nd generation of epigenetic clocks (the latter additionally trained on phenotypic data). Objective: To determine if accelerated epigenetic aging is associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods. Design: Cross-sectional My Body My Story Study (MBMS; US, 2008-2010) and Exam 5 Multi-Ethnic Atherosclerosis Study (MESA; US, 2010-2012). MBMS DNA extraction: 2021; linkage of structural measures to MBMS and MESA: 2022. Setting: MBMS recruited a random sample of US-born Black non-Hispanic (BNH) and white non-Hispanic (WNH) participants from 4 community health centers in Boston, MA. The MESA Exam 5 epigenetic component included 975 randomly selected US-born BNH, WNH, and Hispanic participants from four field sites: Baltimore, MD; Forsyth County, NC; New York City, NY; St. Paul, MN. Participants: US-born persons (MBMS: 224 BNH, 69 WNH; MESA: 229 BNH, 555 WNH, 191 Hispanic). Main outcome and measures: 10 epigenetic clocks (six 1st generation; four 2nd generation), computed using DNA methylation data (DNAm) from blood spots (MBMS; N = 293) and purified monocytes (MESA; N = 975). Results: Among Black non-Hispanic MBMS participants, epigenetic age acceleration was associated with being born in a Jim Crow state by 0.14 standard deviations (95% confidence interval [CI] 0.00, 0.27) and with birth state conservatism (0.06, 95% CI 0.00, 0.05), pooling across all clocks, as was low parental education for both Black non-Hispanic and white non-Hispanic MBMS participants (respectively: 0.24, 95% CI 0.08, 0.39, and 0.27, 95% CI 0.03, 0.51. Adult impoverishment was positively associated with the pooled 2nd generation clocks among the MESA participants (Black non-Hispanic: 0.06, 95% CI 0.01, 0.12; white non-Hispanic: 0.05, 95% CI 0.01, 0.08; Hispanic: 0.07, 95% CI 0.01, 0.14). Conclusions and Relevance: Epigenetic accelerated aging may be one of the biological mechanisms linking exposure to racialized and economic injustice to well-documented inequities in premature morbidity and mortality.

An epigenome-wide analysis of DNA methylation, racialized and economic inequities, and air pollution.

Importance: DNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination. Objective: Our study tests the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied. Design: A series of cross-sectional EWAS, conducted in My Body My Story (MBMS, biological specimens collected 2008-2010, DNAm assayed in 2021); and the Multi Ethnic Study of Atherosclerosis (MESA; biological specimens collected 2010-2012, DNAm assayed in 2012-2013); using new georeferenced social exposure data for both studies (generated in 2022). Setting: MBMS was recruited from four community health centers in Boston; MESA was recruited from four field sites in: Baltimore, MD; Forsyth County, NC; New York City, NY; and St. Paul, MN. Participants: Two population-based samples of US-born Black non-Hispanic (Black NH), white non-Hispanic (white NH), and Hispanic individuals (MBMS; n=224 Black NH and 69 white NH) and (MESA; n=229 Black NH, n=555 white NH and n=191 Hispanic). Exposures: Eight social exposures encompassing racial discrimination, economic adversity, and air pollution. Main outcome: Genome-wide changes in DNAm, as measured using the Illumina EPIC BeadChip (MBMS; using frozen blood spots) and Illumina 450k BeadChip (MESA; using purified monocytes). Our hypothesis was formulated after data collection. Results: We observed the strongest associations with traffic-related air pollution (measured via black carbon and nitrogen oxides exposure), with evidence from both studies suggesting that air pollution exposure may induce epigenetic changes related to inflammatory processes. We also found suggestive associations of DNAm variation with measures of structural racial discrimination (e.g., for Black NH participants, born in a Jim Crow state; adult exposure to racialized economic residential segregation) situated in genes with plausible links to effects on health. Conclusions and Relevance: Overall, this work suggests that DNAm is a biological mechanism through which structural racism and air pollution become embodied and may lead to health inequities.