Socioeconomic inequalities in molecular risk for chronic diseases observed in young adulthood.

Many common chronic diseases of aging are negatively associated with socioeconomic status (SES). This study examines whether inequalities can already be observed in the molecular underpinnings of such diseases in the 30s, before many of them become prevalent. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a large, nationally representative sample of US subjects who were followed for over two decades beginning in adolescence. We now have transcriptomic data (mRNA-seq) from a random subset of 4,543 of these young adults. SES in the household-of-origin and in young adulthood were examined as covariates of a priori-defined mRNA-based disease signatures and of specific gene transcripts identified de novo. An SES composite from young adulthood predicted many disease signatures, as did income and subjective status. Analyses highlighted SES-based inequalities in immune, inflammatory, ribosomal, and metabolic pathways, several of which play central roles in senescence. Many genes are also involved in transcription, translation, and diverse signaling mechanisms. Average causal-mediated effect models suggest that body mass index plays a key role in accounting for these relationships. Overall, the results reveal inequalities in molecular risk factors for chronic diseases often decades before diagnoses and suggest future directions for social signal transduction models that trace how social circumstances regulate the human genome.

Material hardship and telomere length in children.

Telomere length (TL) serves as a biomarker of exposure to stressors, including material hardship. Data from the Future of Families and Child Wellbeing Study (1998-2015) were utilized to determine whether prior material hardship was associated with shorter salivary TL at years 9 and 15. 49% of the year 9 study population were female, 49% were Black, and 25% were Hispanic. At year 9 (N = 1990), regression analyses found a significant association between prior material hardship and shorter TL (ß = -.005, p < .01). Additionally, at year 15 (N = 1874), material hardship experienced during infancy and toddlerhood was associated with shorter TL (ß = -.009, p < .01), pointing toward infancy and toddlerhood as a sensitive period.

Institutional Context Shapes the Physical Health of College Graduates Differently for U.S. White, Black, and Hispanic Adults.

Greater educational attainment is generally associated with healthier and longer lives. However, important heterogeneity in who benefits from educational attainment, how much, and why remains underexplored. In particular, in the United States, the physical health returns to educational attainment are not as large for minoritized racial and ethnic groups compared with individuals racialized as White. Yet, our current understanding of ethnoracial differences in educational health disparities is limited by an almost exclusive focus on the quantity of education attained without sufficient attention to heterogeneity within educational attainment categories, such as different institution types among college graduates. Using biomarker data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we test whether the physical health of college graduates in early adulthood (aged 24-32) varies by institution type and for White, Black, and Hispanic adults. In considering the role of the college context, we conceptualize postsecondary institutions as horizontally stratified and racialized institutional spaces with different implications for the health of their graduates. Finally, we quantify the role of differential attendance at and returns to postsecondary institution type in shaping ethnoracialized health disparities among college graduates in early adulthood.

Taking John Schulenberg's "long view" on successful transitions to adulthood: Associations with adult substance use.

Can positive transitions into young adulthood at age 25 prevent problematic substance use at age 31, even in the context of childhood adverse family environments, conduct problems, and adolescent substance use? We lean on John Schulenberg's developmental framework to examine this question, focusing on the potential young adult milestones of high school and college graduation, employment, residential independence, romantic partnership, and parenthood. Data came from a prospective-longitudinal multi-method study with N = 1199 participants who were first assessed at age 5 years old and followed to age 31. An accumulation of positive transitions in young adulthood (age 25) was associated with lower likelihood of age 31 problematic cannabis use. The protective effect for problematic cannabis use remained even when adjusting for childhood adverse family environments and was primarily driven by successful college graduation and/or home ownership. The accumulation of positive transitions protected individuals at modest to somewhat elevated risk due to childhood adverse family environments from experiencing age 31 cannabis use problems. However, for other individuals with very high numbers of conduct problems, or with high levels of adolescent substance use, the protective effects of accumulated positive transitions to young adulthood were less strong or nonexistent. Moreover, individuals who completed college or obtained full-time employment by 25 were more likely to report problematic age 31 alcohol use. These findings highlight the central tenets of John Schulenberg's developmental framework, including the examination of ontogenetic continuity and discontinuity, the interplay of developmentally distal and proximal effects, and the identification of developmental protective factors that may sway people toward or away from substance use.

Socioeconomic Inequalities and Molecular Risk for Aging in Young Adulthood.

Diverse manifestations of biological aging often reflect disparities in socioeconomic status (SES). In this paper, we examine associations between indicators of SES and an mRNA-based aging signature during young adulthood, before clinical indications of aging are common. We use data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adults aged 33-43 years, with transcriptomic data from a subset of 2,491 participants. Biological aging is measured using 1) a composite transcriptomic aging signature previously identified by Peters et al.'s out-of-sample meta-analysis (Nat Commun. 2015;6:8570) and 2) 9 subsets that represent functional pathways of coexpressed genes. SES refers to income, education, occupation, subjective social status, and a composite measure combining these 4 dimensions. We examine hypothesized mechanisms through which SES could affect aging: body mass index, smoking, health insurance status, difficulty paying bills, and psychosocial stress. We find that SES-especially the composite measure and income-is associated with transcriptomic aging and immune, mitochondrial, ribosomal, lysosomal, and proteomal pathways. Counterfactual mediational models suggest that the mediators partially account for these associations. The results thus reveal that numerous biological pathways associated with aging are already linked to SES in young adulthood.

Population-based RNA profiling in Add Health finds social disparities in inflammatory and antiviral gene regulation to emerge by young adulthood.

Health in later life varies significantly by individual demographic characteristics such as age, sex, and race/ethnicity, as well as by social factors including socioeconomic status and geographic region. This study examined whether sociodemographic variations in the immune and inflammatory molecular underpinnings of chronic disease might emerge decades earlier in young adulthood. Using data from 1,069 young adults from the National Longitudinal Study of Adolescent to Adult Health (Add Health)-the largest nationally representative and ethnically diverse sample with peripheral blood transcriptome profiles-we analyzed variation in the expression of genes involved in inflammation and type I interferon (IFN) response as a function of individual demographic factors, sociodemographic conditions, and biobehavioral factors (smoking, drinking, and body mass index). Differential gene expression was most pronounced by sex, race/ethnicity, and body mass index (BMI), but transcriptome correlates were identified for every demographic dimension analyzed. Inflammation-related gene expression showed the most pronounced variation as a function of biobehavioral factors (BMI and smoking) whereas type I IFN-related transcripts varied most strongly as a function of individual demographic characteristics (sex and race/ethnicity). Bioinformatic analyses of transcription factor and immune-cell activation based on transcriptome-wide empirical differences identified additional effects of family poverty and geographic region. These results identify pervasive sociodemographic differences in immune-cell gene regulation that emerge by young adulthood and may help explain social disparities in the development of chronic illness and premature mortality at older ages.

Contextualizing Educational Disparities in Health: Variations by Race/Ethnicity, Nativity, and County-Level Characteristics.

Educational disparities in health are well documented, yet the education-health relationship is inconsistent across racial/ethnic and nativity groups. These inconsistencies may arise from characteristics of the early life environments in which individuals attain their education. We evaluate this possibility by investigating (1) whether educational disparities in cardiometabolic risk vary by race/ethnicity and nativity among Black, Hispanic, and White young adults; (2) the extent to which racial/ethnic-nativity differences in the education-health relationship are contingent on economic, policy, and social characteristics of counties of early life residence; and (3) the county characteristics associated with the best health at higher levels of education for each racial/ethnic-nativity group. Using data from the National Longitudinal Study of Adolescent to Adult Health, we find that Black young adults who achieve high levels of education exhibit worse health across a majority of contexts relative to their White and Hispanic counterparts. Additionally, we observe more favorable health at higher levels of education across almost all contexts for White individuals. For all other racial/ethnic-nativity groups, the relationship between education and health depends on the characteristics of the early life counties of residence. Findings highlight place-based factors that may contribute to the development of racial/ethnic and nativity differences in the education-health relationship among U.S. young adults.

The Early Life Course of Body Weight and Gene Expression Signatures for Disease.

We examined the way body-weight patterns through the first 4 decades of life relate to gene expression signatures of common forms of morbidity, including cardiovascular disease (CVD), type 2 diabetes (T2D), and inflammation. As part of wave V of the nationally representative National Longitudinal Study of Adolescent to Adult Health (1997-2018) in the United States, mRNA abundance data were collected from peripheral blood (n = 1,132). We used a Bayesian modeling strategy to examine the relative associations between body size at 5 life stages-birth, adolescence, early adulthood, young adulthood, and adulthood-and gene expression-based disease signatures. We compared life-course models that consider critical or sensitive periods, as well as accumulation over the entire period. Our results are consistent with a sensitive-period model when examining CVD and T2D gene expression signatures: Birth weight has a prominent role for the CVD and T2D signatures (explaining 33.1% and 22.1%, respectively, of the total association accounted for by body size), while the most recent adult obesity status (ages 33-39) is important for both of these gene expression signatures (24.3% and 35.1%, respectively). Body size in all life stages was associated with inflammation, consistent with the accumulation model.

College completion predicts lower depression but higher metabolic syndrome among disadvantaged minorities in young adulthood.

Individuals with higher educational attainment live healthier and longer lives. However, not everyone benefits equally from higher education. In particular, the black-white gap in life expectancy is greater at higher levels of educational attainment. Furthermore, recent research suggests that disadvantaged African Americans in the rural Southeast who attend college have worse physical health than their similarly disadvantaged peers who do not attend college. The extent to which this pattern generalizes to a nationally representative, mixed-race sample is unknown. Using data from the National Longitudinal Study of Adolescent to Adult Health, we test whether the health benefits associated with college completion vary by level of childhood disadvantage for depression and metabolic syndrome in young adulthood, across race/ethnicity. We find uniform lower depression associated with college completion regardless of childhood disadvantage, and across non-Hispanic white, non-Hispanic black, and Hispanic young adults. College completion is associated with lower metabolic syndrome for whites across all levels of childhood disadvantage. In contrast, college completion is associated with higher metabolic syndrome among black and Hispanic young adults from disadvantaged childhood environments. Our findings suggest that, for minorities from disadvantaged backgrounds, finishing college pays substantial dividends for mental health but simultaneously exacts costs with regard to physical health. This pattern contrasts starkly with whites and minorities from more privileged backgrounds, for whom college completion is associated with benefits to both mental and physical health. These results suggest that racial disparities in health may persist in part because the health of upwardly mobile minorities is compromised in young adulthood.

The Depths of Despair Among US Adults Entering Midlife.

OBJECTIVES: To test whether indicators of despair are rising among US adults as they age toward midlife and whether this rise is concentrated among low-educated Whites and in rural areas. METHODS: We used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of US adolescents in 1994. Our sample was restricted to individuals who participated in 1 or more of 5 waves (1994-2017) and self-identified as non-Hispanic White, non-Hispanic Black, or Hispanic (n = 18 446). We examined change in indicators of despair from adolescence to adulthood using multilevel regression analysis, testing for differences by race/ethnicity, education, and rurality. RESULTS: We found evidence of rising despair among this cohort over the past decade. This increase was not restricted to low-educated Whites or to rural areas. CONCLUSIONS: Results suggest that generally rising despair among the young adult cohort now reaching midlife that cuts across racial/ethnic, educational, and geographic groups may presage rising midlife mortality for these subgroups in the next decade.

Does Despair Really Kill? A Roadmap for an Evidence-Based Answer.

Two seemingly associated demographic trends have generated considerable interest: income stagnation and rising premature mortality from suicides, drug poisoning, and alcoholic liver disease among US non-Hispanic Whites with low education. Economists interpret these population-level trends to indicate that despair induced by financial stressors is a shared pathway to these causes of death. Although we now have the catchy term "deaths of despair," we have yet to study its central empirical claim: that conceptually defined and empirically assessed "despair" is indeed a common pathway to several causes of death. At the level of the person, despair consists of cognitive, emotional, behavioral, and biological domains. Despair can also permeate social relationships, networks, institutions, and communities. Extant longitudinal data sets feature repeated measures of despair-before, during, and after the Great Recession-offering resources to test the role that despair induced by economic decline plays in premature morbidity and mortality. Such tests must also focus on protective factors that could shield individuals. Deaths of despair is more than a phrase; it constitutes a hypothesis that deserves conceptual mapping and empirical study with longitudinal, multilevel data.

Father Absence and Accelerated Reproductive Development in Non-Hispanic White Women in the United States.

Girls who experience father absence in childhood also experience accelerated reproductive development in comparison with peers with present fathers. One hypothesis advanced to explain this empirical pattern is genetic confounding, wherein gene-environment correlation (rGE) causes a spurious relationship between father absence and reproductive timing. We test this hypothesis by constructing polygenic scores for age at menarche and first birth using recently available genome-wide association study results and molecular genetic data on a sample of non-Hispanic white females from the National Longitudinal Study of Adolescent to Adult Health. We find that young women's accelerated menarche polygenic scores are unrelated to their exposure to father absence. In contrast, polygenic scores for earlier age at first birth tend to be higher in young women raised in homes with absent fathers. Nevertheless, father absence and the polygenic scores independently and additively predict reproductive timing. We find no evidence in support of the rGE hypothesis for accelerated menarche and only limited evidence in support of the rGE hypothesis for earlier age at first birth.

Childhood Risk of Parental Absence in Tanzania.

Although parents might not live with their children for a variety of reasons, existing accounts of parental absence often examine one cause in isolation. Using detailed longitudinal demographic surveillance data from Rufiji, Tanzania, this article examines parental absence due to death, migration, child relocation, union dissolution, and union formation from 2001-2011. Employing survival analysis, the article quantifies children's risk of absence by cause and investigates sociodemographic variation in this risk. Of children born into two-parent households, 25% experience maternal absence by age 10, and 40% experience paternal absence by the same age. Roughly one-quarter of children are born into single-mother families with an absent father at birth, and nearly 70% of these children experience maternal absence as well by age 10. Despite the emphasis on orphanhood in the research and policy communities, parental death is the least common cause of absence. Furthermore, although demographic and socioeconomic characteristics are strong predictors of absence, variation in these relationships across causes underscores the distinctiveness and similarity of different reasons for absence.

Female migrants, family members and community socio-demographic characteristics influence facility delivery in Rufiji, Tanzania.

BACKGROUND: Health professionals and public health experts in maternal and newborn health encourage women to deliver at health facilities in an effort to reduce maternal and newborn mortality. In the existing literature, there is scant information on how migration, family members and community influence facility delivery. This study addresses this knowledge gap using 10 years of longitudinal surveillance data from a rural district of Tanzania. METHODS: Multilevel logistic regression was used to quantify the influence of hypothesized migration, family and community-level factors on facility delivery while adjusting for known confounders identified in the literature. We report adjusted odds ratios (AOR). RESULTS: Overall, there has been an increase of 14% in facility delivery over the ten years, from 63% in 2001 to 77% in 2010 (p < .001). Women residing in households with female migrants from outside their community were more likely to give birth in a facility AOR = 1.2 (95% CI 1.11-1.29). Furthermore, the previous facility delivery of sisters and sisters-in-law has a significant influence on women's facility delivery; AOR = 1.29, 95% CI 1.15-1.45 and AOR = 1.7, 95% CI 1.35-2.13 respectively. Community level characteristics play a role as well; women in communities with higher socioeconomic status and older women of reproductive age had increased odds of facility delivery; AOR = 2.37, 95% CI 1.88-2.98 and AOR = 1.17, 95% CI 1.03-1.32 respectively. CONCLUSION: Although there has been an increase in facility delivery over the last decade in Rufiji, this study underscores the importance of female migrants, family members and community in influencing women's place of delivery. The findings of this study suggest that future interventions designed to increase facility delivery must integrate person-to-person facility delivery promotion, especially through women of the community and within families. Furthermore, the results suggest that investment in formal education of the community and increased community socio-economic status may increase facility delivery.

Structural racism in primary schools and changes in epigenetic age acceleration among Black and White youth.

Structural racism generates racial inequities in U.S. primary education, including segregated schools, inequitable funding and resources, racial disparities in discipline and achievement, and hostile racial climates, which are risk factors for adverse youth health and development. Black youth are disproportionately exposed to adverse school contexts that may become biologically embedded via stress-mediated epigenetic pathways. This study examined whether childhood exposure to adverse school contexts is associated with changes in epigenetic aging during adolescent development. DNA methylation-based epigenetic clocks were calculated from saliva samples at ages 9 and 15 among Black (n = 774) and White (n = 287) youth in the Future of Families and Child Wellbeing Study (2009-2015). We performed latent class analyses to identify race-specific primary school contexts using administrative data on segregation, discipline, achievement, resources, economic disadvantage, and racial harassment. We then estimated change in epigenetic age acceleration from childhood to adolescence across school typologies using GrimAge, PhenoAge, and DunedinPACE epigenetic clocks. Three distinct school contexts were identified for Black youth: segregated and highly-disadvantaged (17.0%), segregated and moderately-disadvantaged (52.1%), and integrated and moderately-disadvantaged (30.8%). Two school contexts emerged for White youth: integrated and unequal (46.5%) and predominantly White & advantaged (53.5%). At age 15, Black youth who attended segregated and highly-disadvantaged primary schools experienced increases in their speed of epigenetic aging with GrimAge and DunedinPACE. Slowed epigenetic aging with GrimAge was observed for Black youth who attended integrated and moderately-disadvantaged schools. School contexts were not associated with changes in epigenetic age acceleration for White youth. Our findings suggest that manifestations of structural racism in primary school contexts are associated with early-life epigenetic age acceleration and may forecast future health inequities.

The Sociodemographic and Lifestyle Correlates of Epigenetic Aging in a Nationally Representative U.S. Study of Younger Adults.

Importance: Epigenetic clocks represent molecular evidence of disease risk and aging processes and have been used to identify how social and lifestyle characteristics are associated with accelerated biological aging. However, most of this research is based on older adult samples who already have measurable chronic disease. Objective: To investigate whether and how sociodemographic and lifestyle characteristics are related to biological aging in a younger adult sample across a wide array of epigenetic clock measures. Design: Nationally representative prospective cohort study. Setting: United States (U.S.). Participants: Data come from the National Longitudinal Study of Adolescent to Adult Health, a national cohort of adolescents in grades 7-12 in U.S. in 1994 followed for 25 years over five interview waves. Our analytic sample includes participants followed-up through Wave V in 2016-18 who provided blood samples for DNA methylation (DNAm) testing (n=4237) at Wave V. Exposure: Sociodemographic (sex, race/ethnicity, immigrant status, socioeconomic status, geographic location) and lifestyle (obesity status, exercise, tobacco, and alcohol use) characteristics. Main Outcome: Biological aging assessed from blood DNAm using 16 epigenetic clocks when the cohort was aged 33-44 in Wave V. Results: While there is considerable variation in the mean and distribution of epigenetic clock estimates and in the correlations among the clocks, we found sociodemographic and lifestyle factors are more often associated with biological aging in clocks trained to predict current or dynamic phenotypes (e.g., PhenoAge, GrimAge and DunedinPACE) as opposed to clocks trained to predict chronological age alone (e.g., Horvath). Consistent and strong associations of faster biological aging were found for those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use. Conclusions and Relevance: Our study found important social and lifestyle factors associated with biological aging in a nationally representative cohort of younger-aged adults. These findings indicate that molecular processes underlying disease risk can be identified in adults entering midlife before disease is manifest and represent useful targets for interventions to reduce social inequalities in heathy aging and longevity. Key Points: Question: Are epigenetic clocks, measures of biological aging developed mainly on older-adult samples, meaningful for younger adults and associated with sociodemographic and lifestyle characteristics in expected patterns found in prior aging research?Findings: Sociodemographic and lifestyle factors were associated with biological aging in clocks trained to predict morbidity and mortality showing accelerated aging among those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use.Meaning: Age-related molecular processes can be identified in younger-aged adults before disease manifests and represent potential interventions to reduce social inequalities in heathy aging and longevity.

Partnership concurrency and coital frequency.

National HIV prevalence estimates across sub-Saharan Africa range from less than 1 percent to over 25 percent. Recent research proposes several explanations for the observed variation, including prevalence of male circumcision, levels of condom use, presence of other sexually transmitted infections, and practice of multiple concurrent partnerships. However, the importance of partnership concurrency for HIV transmission may depend on how it affects coital frequency with each partner. The coital dilution hypothesis suggests that coital frequency within a partnership declines with the addition of concurrent partners. Using sexual behavior data from rural Malawi and urban Kenya, we investigate the relationship between partnership concurrency and coital frequency, and find partial support for the coital dilution hypothesis. We conclude the paper with a discussion of our findings in light of the current literature on concurrency.

Defining despair: Assessing the multidimensionality of despair and its association with suicidality and substance use in early to middle adulthood.

Despite considerable scientific interest in documenting growing despair among U.S. adults, far less attention has been paid to defining despair and identifying appropriate measures. Emerging perspectives from social science and psychiatry outline a comprehensive, multidimensional view of despair, inclusive of individuals' cognitive, emotional, biological and somatic, and behavioral circumstances. The current study assesses the structure and plausibility of this framework based on longitudinal data spanning early to middle adulthood. We identified 40 measures of different dimensions of despair in Wave IV (2008-2009) of the National Longitudinal Study of Adult to Adolescent Health (n = 9149). We used structural equation modeling to evaluate hypothesized relationships among observed and latent variables; we then regressed Wave V (2016-2018) suicidality, heavy drinking, marijuana use, prescription drug misuse, and illicit drug use on latent despair. Our analyses find that models for separate dimensions of despair and overall despair demonstrated excellent fit. Overall despair was a significant predictor of Wave V outcomes, especially suicidality, accounting for 20% of its variation, as compared to 1%-7% of the variation in substance use. Suicidality was consistently associated with all domains of despair; behavioral despair explained the most variation in substance use. Given these results we contend that, lacking direct measures, latent despair can be modeled using available survey items; however, some items are likely better indicators of latent dimensions of despair than others. Moreover, the association between despair and key health behaviors varies considerably, challenging its status as a mechanism simultaneously underlying increased substance use and suicide mortality in the United States. Critically, further validation of measures in other surveys can improve the operationalization of despair and its associated conceptual and theoretical frameworks, thus advancing our understanding of this concept.

Midlife Health in Britain and the US: A comparison of Two Nationally Representative Cohorts.

Background: Older adults in the United States (US) have worse health and wider socioeconomic inequalities in health compared to Britain. Less is known about how health in the two countries compares in midlife, a time of emerging health decline, including inequalities in health. Methods: We compare measures of smoking status, alcohol consumption, obesity, self-rated health, cholesterol, blood pressure, and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N= 9,665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the US (N=12,297), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. Findings: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health, heavy drinking, and smoking was worse in Britain. We found smaller socioeconomic inequalities in midlife health in Britain compared to the US. For some outcomes (e.g., smoking), the most socioeconomically advantaged group in the US was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. Interpretation: US adults have worse cardiometabolic health than British counterparts, even in early midlife. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems, or other environmental risk factors. Funding: ESRC, UKRI, MRC, NIH, European Research Council, Leverhulme Trust.