Socioeconomic inequalities in early adulthood disrupt the immune transcriptomic landscape via upstream regulators.

Disparities in socio-economic status (SES) predict many immune system-related diseases, and previous research documents relationships between SES and the immune cell transcriptome. Drawing on a bioinformatically-informed network approach, we situate these findings in a broader molecular framework by examining the upstream regulators of SES-associated transcriptional alterations. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 4543 adults in the United States. Results reveal a network-of differentially expressed genes, transcription factors, and protein neighbors of transcription factors-that shows widespread SES-related dysregulation of the immune system. Mediational models suggest that body mass index (BMI) plays a key role in accounting for many of these associations. Overall, the results reveal the central role of upstream regulators in socioeconomic differences in the molecular basis of immunity, which propagate to increase risk of chronic health conditions in later-life.

Socioeconomic inequalities in young adulthood disrupt the immune transcriptomic landscape via upstream regulators.

Disparities in socio-economic status (SES) predict many immune system-related diseases, and previous research documents relationships between SES and the immune cell transcriptome. Drawing on a bioinformatically-informed network approach, we situate these findings in a broader molecular framework by examining the upstream regulators of SES-associated transcriptional alterations. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 4,543 adults in the United States. Results reveal a network-of differentially-expressed genes, transcription factors, and protein neighbors of transcription factors- that shows widespread SES-related dysregulation of the immune system. Mediational models suggest that body mass index plays a key role in accounting for many of these associations. Overall, the results reveal the central role of upstream regulators in socioeconomic differences in the molecular basis of immunity, which propagate to increase risk of chronic health conditions in later-life.

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.

An integrative approach for the analysis of risk and health across the life course: challenges, innovations, and opportunities for life course research.

Life course epidemiology seeks to understand the intricate relationships between risk factors and health outcomes across different stages of life to inform prevention and intervention strategies to optimize health throughout the lifespan. However, extant evidence has predominantly been based on separate analyses of data from individual birth cohorts or panel studies, which may not be sufficient to unravel the complex interplay of risk and health across different contexts. We highlight the importance of a multi-study perspective that enables researchers to: (a) Compare and contrast findings from different contexts and populations, which can help identify generalizable patterns and context-specific factors; (b) Examine the robustness of associations and the potential for effect modification by factors such as age, sex, and socioeconomic status; and (c) Improve statistical power and precision by pooling data from multiple studies, thereby allowing for the investigation of rare exposures and outcomes. This integrative framework combines the advantages of multi-study data with a life course perspective to guide research in understanding life course risk and resilience on adult health outcomes by: (a) Encouraging the use of harmonized measures across studies to facilitate comparisons and synthesis of findings; (b) Promoting the adoption of advanced analytical techniques that can accommodate the complexities of multi-study, longitudinal data; and (c) Fostering collaboration between researchers, data repositories, and funding agencies to support the integration of longitudinal data from diverse sources. An integrative approach can help inform the development of individualized risk scores and personalized interventions to promote health and well-being at various life stages.

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.

Cohort Profile: The Zurich Project on the Social Development from Childhood to Adulthood (z-proso).

The Zurich Project on the Social Development from Childhood to Adulthood (z-proso) began in 2004 in response to the need for a better evidence base to support optimal child social development and prevent crime and violence. Since then, the study has tracked the development of a diverse sample of youths (N = 1,675 in the target sample; ~50% female) from age 7 (n = 1,360) to age 20 (n = 1,180), with primary data collection waves at ages 7, 8, 9, 10, 11, 12, 13, 15, 17, and 20. The study uses a multi-method, multi-informant design that combines teacher, youth, and parent reports with observational and behavioural measures, biosampling, functional imaging, and ecological momentary assessment. Analyses of the data have contributed important evidence to a diversity of topics in child and adolescent development, illuminating the developmental roots of crime and aggression, the impacts of exposure to different forms and combinations of victimisation, and trajectories of mental health and neurodevelopmental symptoms.

Explaining the Occupational Structure of Depressive Symptoms: Precarious Work and Social Marginality across European Countries.

The idea that socioeconomic differences are a "fundamental cause" of health and well-being is the basis for large volumes of research. However, one of the challenges in this area is that of linking socioeconomic positions to etiological mechanisms in theoretically informative ways. The situation is doubly challenging because the expression and meaning of socioeconomic positions and the mechanisms they activate change over time. Focusing on depression and applying mediation analysis to data from a large multinational sample from European countries, we find strong support for a three-stage model where occupational differences are largely mediated by exposure to precarious work, which itself is mediated by social marginality. The model is largely robust across welfare state regimes. Ultimately, the research extends fundamental cause perspectives by highlighting connections between "old" and "new" dimensions of socioeconomic status and the social and social psychological sequelae that connect them to psychological well-being.

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.

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.

Attractiveness Compensates for Low Status Background in the Prediction of Educational Attainment.

BACKGROUND: People who are perceived as good looking or as having a pleasant personality enjoy many advantages, including higher educational attainment. This study examines (1) whether associations between physical/personality attractiveness and educational attainment vary by parental socioeconomic resources and (2) whether parental socioeconomic resources predict these forms of attractiveness. Based on the theory of resource substitution with structural amplification, we hypothesized that both types of attractiveness would have a stronger association with educational attainment for people from disadvantaged backgrounds (resource substitution), but also that people from disadvantaged backgrounds would be less likely to be perceived as attractive (amplification). METHODS: This study draws on data from the National Longitudinal Study of Adolescent to Adult Health-including repeated interviewer ratings of respondents' attractiveness-and trait-state structural equation models to examine the moderation (substitution) and mediation (amplification) of physical and personality attractiveness in the link between parental socioeconomic resources and educational attainment. RESULTS: Both perceived personality and physical attractiveness have stronger associations with educational attainment for people from families with lower levels of parental education (substitution). Further, parental education and income are associated with both dimensions of perceived attractiveness, and personality attractiveness is positively associated with educational attainment (amplification). Results do not differ by sex and race/ethnicity. Further, associations between perceived attractiveness and educational attainment remain after accounting for unmeasured family-level confounders using a sibling fixed-effects model. CONCLUSIONS: Perceived attractiveness, particularly personality attractiveness, is a more important psychosocial resource for educational attainment for people from disadvantaged backgrounds than for people from advantaged backgrounds. People from disadvantaged backgrounds, however, are less likely to be perceived as attractive than people from advantaged backgrounds.

Parental and adolescent health behaviors and pathways to adulthood.

This paper examines associations among parental and adolescent health behaviors and pathways to adulthood. Using data from the National Longitudinal Study of Adolescent to Adult Health, we identify a set of latent classes describing pathways into adulthood and examine health-related predictors of these pathways. The identified pathways are consistent with prior research using other sources of data. Results also show that both adolescent and parental health behaviors differentiate pathways. Parental and adolescent smoking are associated with lowered probability of the higher education pathway and higher likelihood of the work and the work & family pathways (entry into the workforce soon after high school completion). Adolescent drinking is positively associated with the work pathway and the higher education pathway, but decreases the likelihood of the work & family pathway. Neither parental nor adolescent obesity are associated with any of the pathways to adulthood. When combined, parental/adolescent smoking and adolescent drinking are associated with displacement from the basic institutions of school, work, and family.

Sex Differences in Associations Between Subjective Social Status and C-Reactive Protein in Young Adults.

OBJECTIVE: In middle-aged and older samples, perceived subjective socioeconomic status (SSS) is a marker of social rank that is associated with elevated inflammation and cardiovascular disease risk independent of objective indicators of SES (oSES). Whether SSS is uniquely associated with elevated inflammation during young adulthood and whether these linkages differ by sex have not been studied using a nationally representative sample of young adults. METHODS: Data came from the National Longitudinal Study of Adolescent to Adult Health. At Wave IV, young adults aged mostly 24 to 32 years reported their SSS, oSES, and a range of covariates of both SES and elevated inflammation. Trained fieldworkers assessed medication use, body mass index, and waist circumference, and also collected bloodspots from which high-sensitivity C-reactive protein (hs-CRP) was assayed. The sample size for the present analyses was n = 13,236. RESULTS: Descriptive and bivariate analyses revealed a graded association between SSS and hs-CRP (b = -0.072, standard error [SE] = 0.011, p < .001): as SSS declined, mean levels of hs-CRP increased. When oSES indicators were taken into account, this association was no longer significant in women (b = -0.013, SE = 0.019, p = .514). In men, a small but significant SSS-hs-CRP association remained after adjusting for oSES indicators and additional potential confounders of this association in the final models (b = -0.034, SE = 0.011 p = .003; p < .001 for the sex by SSS interaction). CONCLUSIONS: SSS is independently associated with elevated inflammation in young adults. The associations were stronger in men than in women. These data suggest that subjective, global assessments of social rank might play a role in developing adverse health outcomes.

The Sequencing of a College Degree during the Transition to Adulthood: Implications for Obesity.

In this study we consider the health implications of the sequencing of a college degree vis-à-vis familial roles during the transition to adulthood. We hypothesize that people who earned a college degree before assuming familial roles will have better health than people who earned a college degree afterwards. To test this hypothesis, we focus on obesity and use data from the National Longitudinal Study of Adolescent Health. Results show that marriage before completion of college was associated with a 50% higher probability of becoming obese when compared with marriage after completion of college. Parenthood before college completion was associated with a greater than twofold increase in the probability of becoming obese when compared to parenthood afterwards for black men. These findings suggest that the well-established association of education with health depends on its place in a sequence of roles.

A discrete-time Multiple Event Process Survival Mixture (MEPSUM) model.

Traditional survival analysis was developed to investigate the occurrence and timing of a single event, but researchers have recently begun to ask questions about the order and timing of multiple events. A multiple event process survival mixture model is developed here to analyze nonrepeatable events measured in discrete-time that may occur at the same point in time. Building on both traditional univariate survival analysis and univariate survival mixture analysis, the model approximates the underlying multivariate distribution of hazard functions via a discrete-point finite mixture in which the mixing components represent prototypical patterns of event occurrence. The model is applied in an empirical analysis concerning transitions to adulthood, where the events under study include parenthood, marriage, beginning full-time work, and obtaining a college degree. Promising opportunities, as well as possible limitations of the model and future directions for research, are discussed.

Conscientiousness, health, and aging: the life course of personality model.

The Conscientiousness (C) of the self and significant others influences health by way of mediational chains involving socioeconomic attainment, the avoidance and neutralization of stressors, the promotion of health behaviors and the minimization of risk behaviors, and the management of symptoms and diseases. Yet, meta-analyses reveal that these associations are moderated by factors that are not well understood. We propose the Life Course of Personality Model (LCP Model), which comprises a series of hypotheses that suggest how such mediational chains are subject to 2 sources of contingency. First, the mechanisms by which C translates into health and the avoidance of risk change from early childhood to late adulthood, involving processes that are specific to phases of the life course; also, however, C influences health by way of continuous processes extending over many decades of life. Second, C may be more consequential in some social contexts than in others, and when accompanied by some constellations of personality characteristics than by others. That is, the mediational processes by which C translates into health and the avoidance of disease are likely moderated by timing, social context (including the C of others), and other aspects of the individual's personality. We consider methodological implications of the LCP Model.

Psychometric properties of the mini-IPIP in a large, nationally representative sample of young adults.

Drawing on a large, nationally representative sample of young adults (the National Longitudinal Study of Adolescent Health; N = 15,701; M age = 29.10), we evaluated the psychometric properties of the Mini-IPIP, a 20-item inventory designed to concisely assess the 5 factors of personality. The results suggest that the Mini-IPIP has a 5-factor structure; most of the scales have acceptable reliability; all the scales have partial or full metric invariance; and the scales exhibit some degree of criterion validity. However, the absence of scalar invariance for many of the scales suggests caution when comparing personality scores among groups defined by sex or race and ethnicity. We offer practical considerations for researchers interested in using this inventory with this sample, and also suggestions for modification of the Mini-IPIP.

Evocative gene-parenting correlations and academic performance at first grade: an exploratory study.

Academic performance during the first years of school lays the groundwork for subsequent trajectories of academic success throughout childhood and adolescence. The current study tests a model according to which a gene-parenting correlation in the first 3 years of life is associated with subsequent psychosocial adjustment and then academic performance in the first grade (as indicated by teachers' assessment of academic behavior and two subscales of the Woodcock-Johnson Test of Achievement, Third Edition). Drawing on multiple waves of data from the Durham Child Health and Development Study, we find that risk alleles for dopamine receptor genes (dopamine receptor D4 for girls, dopamine receptor D2 for boys) are associated with less sensitive parenting. For girls, parenting mediates the link between dopamine receptor D4 and all academic outcomes. There is some indication that parenting also influences girls' withdrawn behavior in the classroom, which in turn influences teachers' assessments of academic performance. For boys, some evidence suggests that parenting is associated with emotion regulation, which is associated with teachers' assessments of academic behavior and both subscales of the Woodcock-Johnson. Replications of this exploratory study are necessary, but these findings provide a first step in understanding how evocative correlations in the home may predict indicators of psychosocial adjustment that in turn influence performance and achievement at school.

The association between parent's health and the educational attainment of their children.

In this paper we compare the educational attainment of adults who had relatively unhealthy parents when they were adolescents to those whose parents were relatively healthy during this time of their lives. We use data from the National Longitudinal Study of Adolescent Health (n = 13,556) to show that U.S. adolescents whose parents described their health as "fair" or "poor" at Wave 1 of the study were more likely to drop out of high school compared to those whose parents reported better levels of health. We do not observe any association between parental health and the likelihood of attending college among those who graduated from high school, however we do show that completing college (among college attendees) is more likely among those whose parents reported better health when they were adolescents. This association persists despite a wide range of statistical controls including socioeconomic status of the household, the physical and mental health status of the respondent, the grade point average of the respondent, the health behaviors of parents, as well as parental time investment. These findings add an important intergenerational component to research on the relationship between socioeconomic status and health.

A life course model of self-rated health through adolescence and young adulthood.

This paper proposes and tests a life course model of self-rated health (SRH) extending from late childhood to young adulthood, drawing on three waves of panel data from the National Longitudinal Study of Adolescent Health (Add Health). Very little research has examined SRH during the early decades, or whether and how these self-assessments reflect experiences in the family of origin. Background characteristics (parental education, income, and family structure), parental health conditions (asthma, diabetes, obesity, migraines), and early health challenges (physical abuse, presence of a disability, and parental alcoholism and smoking) predict SRH from adolescence to young adulthood. These experiences in the family-of-origin are substantially mediated by the young person's health and health behaviors (as indicated by obesity, depression, smoking, drinking, and inactivity), although direct effects remain (especially for early health challenges). Associations between SRH and these mediators (especially obesity) strengthen with age. In turn, efforts to promote healthy behaviors in young adulthood, after the completion of secondary school, may be especially strategic in the promotion of health in later adulthood.