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.

Integrative genome-scale analyses reveal post-transcriptional signatures of early human small intestinal development in a directed differentiation organoid model.

BACKGROUND: MicroRNAs (miRNAs) are important post-transcriptional gene regulators controlling cellular lineage specification and differentiation during embryonic development, including the gastrointestinal system. However, miRNA-mediated regulatory mechanisms involved in early embryonic development of human small intestine (SI) remains underexplored. To explore candidate roles for miRNAs in prenatal SI lineage specification in humans, we used a multi-omic analysis strategy in a directed differentiation model that programs human pluripotent stem cells toward the SI lineage. RESULTS: We leveraged small RNA-seq to define the changing miRNA landscape, and integrated chromatin run-on sequencing (ChRO-seq) and RNA-seq to define genes subject to significant post-transcriptional regulation across the different stages of differentiation. Small RNA-seq profiling revealed temporal dynamics of miRNA signatures across different developmental events of the model, including definitive endoderm formation, SI lineage specification and SI regional patterning. Our multi-omic, integrative analyses showed further that the elevation of miR-182 and reduction of miR-375 are key events during SI lineage specification. We demonstrated that loss of miR-182 leads to an increase in the foregut master marker SOX2. We also used single-cell analyses in murine adult intestinal crypts to support a life-long role for miR-375 in the regulation of Zfp36l2. Finally, we uncovered opposing roles of SMAD4 and WNT signaling in regulating miR-375 expression during SI lineage specification. Beyond the mechanisms highlighted in this study, we also present a web-based application for exploration of post-transcriptional regulation and miRNA-mediated control in the context of early human SI development. CONCLUSION: The present study uncovers a novel facet of miRNAs in regulating prenatal SI development. We leveraged multi-omic, systems biology approaches to discover candidate miRNA regulators associated with early SI developmental events in a human organoid model. In this study, we highlighted miRNA-mediated post-transcriptional regulation relevant to the event of SI lineage specification. The candidate miRNA regulators that we identified for the other stages of SI development also warrant detailed characterization in the future.

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.

Comprehensive microRNA analysis across genome-edited colorectal cancer organoid models reveals miR-24 as a candidate regulator of cell survival.

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across different combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.

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.

Multiomic analysis defines the first microRNA atlas across all small intestinal epithelial lineages and reveals novel markers of almost all major cell types.

MicroRNA-mediated regulation is critical for the proper development and function of the small intestinal (SI) epithelium. However, it is not known which microRNAs are expressed in each of the cell types of the SI epithelium. To bridge this important knowledge gap, we performed comprehensive microRNA profiling in all major cell types of the mouse SI epithelium. We used flow cytometry and fluorescence-activated cell sorting with multiple reporter mouse models to isolate intestinal stem cells, enterocytes, goblet cells, Paneth cells, enteroendocrine cells, tuft cells, and secretory progenitors. We then subjected these cell populations to small RNA-sequencing. The resulting atlas revealed highly enriched microRNA markers for almost every major cell type (https://sethupathy-lab.shinyapps.io/SI_miRNA/). Several of these lineage-enriched microRNAs (LEMs) were observed to be embedded in annotated host genes. We used chromatin-run-on sequencing to determine which of these LEMs are likely cotranscribed with their host genes. We then performed single-cell RNA-sequencing to define the cell type specificity of the host genes and embedded LEMs. We observed that the two most enriched microRNAs in secretory progenitors are miR-1224 and miR-672, the latter of which we found is deleted in hominin species. Finally, using several in vivo models, we established that miR-152 is a Paneth cell-specific microRNA.NEW & NOTEWORTHY In this study, first, microRNA atlas (and searchable web server) across all major small intestinal epithelial cell types is presented. We have demonstrated microRNAs that uniquely mark several lineages, including enteroendocrine and tuft. Identification of a key marker of mouse secretory progenitor cells, miR-672, which we show is deleted in humans. We have used several in vivo models to establish miR-152 as a specific marker of Paneth cells, which are highly understudied in terms of microRNAs.

Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota.

BACKGROUND & AIMS: Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD+-dependent protein deacetylase, senses environmental stress to alter intestinal integrity. METHODS: We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1flox/flox mice) and control mice (villin-Cre-, Sirt1flox/flox) on a C57BL/6 background. Acute colitis was induced in some mice by addition of 2.5% dextran sodium sulfate to drinking water for 5-9 consecutive days. Some mice were given antibiotics via their drinking water for 4 weeks to deplete their microbiota. Some mice were fed with a cholestyramine-containing diet for 7 days to sequester their bile acids. Feces were collected and proportions of microbiota were analyzed by 16S rRNA amplicon sequencing and quantitative PCR. Intestines were collected from mice and gene expression profiles were compared by microarray and quantitative PCR analyses. We compared levels of specific mRNAs between colon tissues from age-matched patients with ulcerative colitis (n=10) vs without IBD (n=8, controls). RESULTS: Mice with intestinal deletion of SIRT1 (SIRT1 iKO) had abnormal activation of Paneth cells starting at the age of 5-8 months, with increased activation of NF-κB, stress pathways, and spontaneous inflammation at 22-24 months of age, compared with control mice. SIRT1 iKO mice also had altered fecal microbiota starting at 4-6 months of age compared with control mice, in part because of altered bile acid metabolism. Moreover, SIRT1 iKO mice with defective gut microbiota developed more severe colitis than control mice. Intestinal tissues from patients with ulcerative colitis expressed significantly lower levels of SIRT1 mRNA than controls. Intestinal tissues from SIRT1 iKO mice given antibiotics, however, did not have signs of inflammation at 22-24 months of age, and did not develop more severe colitis than control mice at 4-6 months. CONCLUSIONS: In analyses of intestinal tissues, colitis induction, and gut microbiota in mice with intestinal epithelial disruption of SIRT1, we found this protein to prevent intestinal inflammation by regulating the gut microbiota. SIRT1 might therefore be an important mediator of host-microbiome interactions. Agents designed to activate SIRT1 might be developed as treatments for IBDs.

Personality and the Intergenerational Transmission of Educational Attainment: Evidence from Germany.

Research based in the United States, with its relatively open educational system, has found that personality mediates the relationship between parents' and child's educational attainment and this mediational pattern is especially beneficial to students from less-educated households. Yet in highly structured, competitive educational systems, personality characteristics may not predict attainment or may be more or less consequential at different points in the educational career. We examine the salience of personality in the educational attainment process in the German educational system. Data come from a longitudinal sample of 682 17 to 25 year-olds (54% female) from the 2005 and 2015 German Socio-Economic Panel (SOEP). Results show that adolescent personality traits-openness, neuroticism, and conscientiousness-are associated with educational attainment, but personality plays a negligible role in the intergenerational transmission of education. Personality is influential before the decision about the type of secondary degree that a student will pursue (during adolescence). After that turning point, when students have entered different pathways through the system, personality is less salient. Cross-national comparisons in a life course framework broaden the scope of current research on non-cognitive skills and processes of socioeconomic attainment, alerting the analyst to the importance of both institutional structures and the changing importance of these skills at different points in the life course.

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.

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.

Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2.

Microbial protease-mediated disruption of the intestinal epithelium is a potential mechanism whereby a dysbiotic enteric microbiota can lead to disease. This mechanism was investigated using the colitogenic, protease-secreting enteric microbe Enterococcus faecalis. Caco-2 and T-84 epithelial cell monolayers and the mouse colonic epithelium were exposed to concentrated conditioned media (CCM) from E. faecalis V583 and E. faecalis lacking the gelatinase gene (gelE). The flux of fluorescein isothiocyanate (FITC)-labeled dextran across monolayers or the mouse epithelium following exposure to CCM from parental or mutant E. faecalis strains indicated paracellular permeability. A protease-activated receptor 2 (PAR2) antagonist and PAR2-deficient (PAR2(-/-)) mice were used to investigate the role of this receptor in E. faecalis-induced permeability. Gelatinase (GelE) purified from E. faecalis V583 was used to confirm the ability of this protease to induce epithelial cell permeability and activate PAR2. The protease-mediated permeability of colonic epithelia from wild-type (WT) and PAR2(-/-) mice by fecal supernatants from ulcerative colitis patients was assessed. Secreted E. faecalis proteins induced permeability in epithelial cell monolayers, which was reduced in the absence of gelE or by blocking PAR2 activity. Secreted E. faecalis proteins induced permeability in the colonic epithelia of WT mice that was absent in tissues from PAR2(-/-) mice. Purified GelE confirmed the ability of this protease to induce epithelial cell permeability via PAR2 activation. Fecal supernatants from ulcerative colitis patients induced permeability in the colonic epithelia of WT mice that was reduced in tissues from PAR2(-/-) mice. Our investigations demonstrate that GelE from E. faecalis can regulate enteric epithelial permeability via PAR2.

Mouse Paneth cell antimicrobial function is independent of Nod2.

OBJECTIVE: Although polymorphisms of the NOD2 gene predispose to the development of ileal Crohn's disease, the precise mechanisms of this increased susceptibility remain unclear. Previous work has shown that transcript expression of the Paneth cell (PC) antimicrobial peptides (AMPs) α-defensin 4 and α-defensin-related sequence 10 are selectively decreased in Nod2(-/-) mice. However, the specific mouse background used in this previous study is unclear. In light of recent evidence suggesting that mouse strain strongly influences PC antimicrobial activity, we sought to characterise PC AMP function in commercially available Nod2(-/-) mice on a C57BL/6 (B6) background. Specifically, we hypothesised that Nod2(-/-) B6 mice would display reduced AMP expression and activity. DESIGN: Wild-type (WT) and Nod2(-/-) B6 ileal AMP expression was assessed via real-time PCR, acid urea polyacrylamide gel electrophoresis and mass spectrometry. PCs were enumerated using flow cytometry. Functionally, α-defensin bactericidal activity was evaluated using a gel-overlay antimicrobial assay. Faecal microbial composition was determined using 454-sequencing of the bacterial 16S gene in cohoused WT and Nod2(-/-) littermates. RESULTS: WT and Nod2(-/-) B6 mice displayed similar PC AMP expression patterns, equivalent α-defensin profiles, and identical antimicrobial activity against commensal and pathogenic bacterial strains. Furthermore, minimal differences in gut microbial composition were detected between the two cohoused, littermate mouse groups. CONCLUSIONS: Our data reveal that Nod2 does not directly regulate PC antimicrobial activity in B6 mice. Moreover, we demonstrate that previously reported Nod2-dependent influences on gut microbial composition may be overcome by environmental factors, such as cohousing with WT littermates.

Comprehensive, quantitative bioprocess productivity monitoring using fluorescence EEM spectroscopy and chemometrics.

This study demonstrates the application of fluorescence excitation-emission matrix (EEM) spectroscopy to the quantitative predictive analysis of recombinant glycoprotein production cultured in a Chinese hamster ovary (CHO) cell fed-batch process. The method relies on the fact that EEM spectra of complex solutions are very sensitive to compositional change. As the cultivation progressed, changes in the emission properties of various key fluorophores (e.g., tyrosine, tryptophan, and the glycoprotein product) showed significant differences, and this was used to follow culture progress via multiple curve resolution alternating least squares (MCR-ALS). MCR-ALS clearly showed the increase in the unique dityrosine emission from the product glycoprotein as the process progressed, thus provided a qualitative tool for process monitoring. For the quantitative predictive modelling of process performance, the EEM data was first subjected to variable selection and then using the most informative variables, partial least-squares (PLS) regression was implemented for glycoprotein yield prediction. Accurate predictions with relative errors of between 2.3 and 4.6% were obtained for samples extracted from the 100 to 5000 L scale bioreactors. This study shows that the combination of EEM spectroscopy and chemometric methods of evaluation provides a convenient method for monitoring at-line or off-line the productivity of industrial fed-batch mammalian cell culture processes from the small to large scale. This method has applicability to the advancement of process consistency, early problem detection, and quality-by-design (QbD) practices.

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.

A Bayesian functional approach to test models of life course epidemiology over continuous time.

BACKGROUND: Life course epidemiology examines associations between repeated measures of risk and health outcomes across different phases of life. Empirical research, however, is often based on discrete-time models that assume that sporadic measurement occasions fully capture underlying long-term continuous processes of risk. METHODS: We propose (i) the functional relevant life course model (fRLM), which treats repeated, discrete measures of risk as unobserved continuous processes, and (ii) a testing procedure to assign probabilities that the data correspond to conceptual models of life course epidemiology (critical period, sensitive period and accumulation models). The performance of the fRLM is evaluated with simulations, and the approach is illustrated with empirical applications relating body mass index (BMI) to mRNA-seq signatures of chronic kidney disease, inflammation and breast cancer. RESULTS: Simulations reveal that fRLM identifies the correct life course model with three to five repeated assessments of risk and 400 subjects. The empirical examples reveal that chronic kidney disease reflects a critical period process and inflammation and breast cancer likely reflect sensitive period mechanisms. CONCLUSIONS: The proposed fRLM treats repeated measures of risk as continuous processes and, under realistic data scenarios, the method provides accurate probabilities that the data correspond to commonly studied models of life course epidemiology. fRLM is implemented with publicly-available software.

Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology, and several have been implicated in the pathogenesis of adult CD. However, there is a dearth of large-scale miRNA studies for pediatric CD. We hypothesized that specific miRNAs uniquely mark pediatric CD. We performed small RNA-Seq of patient-matched colon and ileum biopsies from treatment-naive pediatric patients with CD (n = 169) and a control cohort (n = 108). Comprehensive miRNA analysis revealed 58 miRNAs altered in pediatric CD. Notably, multinomial logistic regression analysis revealed that index levels of ileal miR-29 are strongly predictive of severe inflammation and stricturing. Transcriptomic analyses of transgenic mice overexpressing miR-29 show a significant reduction of the tight junction protein gene Pmp22 and classic Paneth cell markers. The dramatic loss of Paneth cells was confirmed by histologic assays. Moreover, we found that pediatric patients with CD with elevated miR-29 exhibit significantly lower Paneth cell counts, increased inflammation scores, and reduced levels of PMP22. These findings strongly indicate that miR-29 upregulation is a distinguishing feature of pediatric CD, highly predictive of severe phenotypes, and associated with inflammation and Paneth cell loss.

Social, behavioral, and genetic linkages from adolescence into adulthood.

The influence of genetic factors on health and behavior is conditioned by social, cultural, institutional, and physical environments in which individuals live, work, and play. We encourage studies supporting multilevel integrative approaches to understanding these contributions to health, and describe the Add Health study as an exemplar. Add Health is a large sample of US adolescents in grades 7 to 12 in 1994-1995 followed into adulthood with 4 in-home interviews and biomarker collections, including DNA. In addition to sampling multiple environments and measuring diverse social and health behavior, Add Health features a fully articulated behavioral genetic sample (3000 pairs) and ongoing genotyping of 12,000 archived samples. We illustrate approaches to understanding health through investigation of the interplay among biological, psychosocial, and physical, contextual, or cultural experiences.

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.

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.