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Background: Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft‐reported inflammatory biomarker C‐reactive protein (CRP). Methods: Prospective study of a population‐representative 1972–1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self‐control. Main adult outcomes were adulthood inflammation measured as suPAR and high‐sensitivity CRP (hsCRP). Results: Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self‐control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001). Conclusions: Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Genetic variants identified in genome-wide association studies of educational attainment have been linked with a range of positive life course development outcomes. However, it remains unclear whether school environments may moderate these genetic associations. We analyze data from two biosocial surveys that contain both genetic data and follow students from secondary school through mid- to late life. We test if the magnitudes of the associations with educational and occupational attainments varied across the secondary schools that participants attended or with characteristics of those schools. Although we find little evidence that genetic associations with educational and occupational attainment varied across schools or with school characteristics, genetic associations with any postsecondary education and college completion were moderated by school-level socioeconomic status. Along similar lines, we observe substantial between-school variation in the average level of educational attainment students achieved for a fixed genotype. These findings emphasize the importance of social context in the interpretation of genetic associations. Specifically, our results suggest that though existing measures of individual genetic endowment have a linear relationship with years of schooling that is relatively consistent across school environments, school context is crucial in connecting an individual's genotype to his or her likelihood of crossing meaningful educational thresholds. [ABSTRACT FROM AUTHOR]

A summary genetic measure, called a "polygenic score," derived from a genome-wide association study (GWAS) of education can modestly predict a person's educational and economic success. This prediction could signal a biological mechanism: Educationlinked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents' position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother's polygenic score predicted her child's attainment over and above the child's own polygenic score, suggesting parents' genetics can also affect their children's attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals' family-oforigin environments and their social mobility. [ABSTRACT FROM AUTHOR]

The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study (New Zealand; persons born 1972-1973). We studied 11 measures in total: telomere-length and erosion, 3 epigenetic-clocks and their ticking rates, and 3 biomarker-composites. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes that geroprotective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-cytosine-phosphateguanine epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect sizes were modest. Results suggested that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials. [ABSTRACT FROM AUTHOR]

Objective: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become "embedded" in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation.Method: The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994-1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime).Results: Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes.Conclusions: Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress. [ABSTRACT FROM AUTHOR]

Humans tend to form social relationships with others who resemble them. Whether this sorting of like with like arises from historical patterns of migration, meso-level social structures in modern society, or individual-level selection of similar peers remains unsettled. Recent research has evaluated the possibility that unobserved genotypes may play an important role in the creation of homophilous relationships. We extend this work by using data from 5,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine genetic similarities among pairs of friends. Although there is some evidence that friends have correlated genotypes, both at the whole-genome level as well as at trait-associated loci (via polygenic scores), further analysis suggests that meso-level forces, such as school assignment, are a principal source of genetic similarity between friends. We also observe apparent social- genetic effects in which polygenic scores of an individual's friends and schoolmates predict the individual's own educational attainment. In contrast, an individual's height is unassociated with the height genetics of peers. [ABSTRACT FROM AUTHOR]

Biological aging measures have been proposed as proxies for extension of healthy life span in trials of geroprotective therapies that aim to slow aging. Several methods to measure biological aging show promise but it is not known if these methods are sensitive to changes caused by geroprotective therapy. We conducted analysis of two proposed methods to quantify biological aging using data from a recently concluded trial of an established geroprotector, caloric restriction. We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N = 220 nonobese adults to 25% caloric restriction (n = 145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n = 75) for 2 years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans. [ABSTRACT FROM AUTHOR]

Socially disadvantaged children face increased morbidity and mortality as they age. Understanding mechanisms through which social disadvantage becomes biologically embedded and devising measurements that can track this embedding are critical priorities for research to address social gradients in health. The analysis by Levine et al. (Am J Epidemiol. 2017;186(5):503-509) of genome-wide gene expression in a subsample of US Health and Retirement Study participants suggests important new directions for the field. Specifically, findings suggest promise in integrating gene expression data into population studies and provide further evidence for the conserved transcriptional response to adversity as a marker of biological embedding of social disadvantage. The study also highlights methodological issues related to the analysis of gene expression data and social gradients in health and a need to examine the conserved transcriptional response to adversity alongside other proposed measurements of biological embedding. Looking to the future, advances in genome science are opening new opportunities for socio-genomic epidemiology. [ABSTRACT FROM AUTHOR]

Importance: Many children in the United States and around the world are exposed to lead, a developmental neurotoxin. The long-term cognitive and socioeconomic consequences of lead exposure are uncertain.Objective: To test the hypothesis that childhood lead exposure is associated with cognitive function and socioeconomic status in adulthood and with changes in IQ and socioeconomic mobility between childhood and midlife.Design, Setting, and Participants: A prospective cohort study based on a population-representative 1972-1973 birth cohort from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (until December 2012).Exposures: Childhood lead exposure ascertained as blood lead levels measured at age 11 years. High blood lead levels were observed among children from all socioeconomic status levels in this cohort.Main Outcomes and Measures: The IQ (primary outcome) and indexes of Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed (secondary outcomes) were assessed at age 38 years using the Wechsler Adult Intelligence Scale-IV (WAIS-IV; IQ range, 40-160). Socioeconomic status (primary outcome) was assessed at age 38 years using the New Zealand Socioeconomic Index-2006 (NZSEI-06; range, 10 [lowest]-90 [highest]).Results: Of 1037 original participants, 1007 were alive at age 38 years, of whom 565 (56%) had been lead tested at age 11 years (54% male; 93% white). Mean (SD) blood lead level at age 11 years was 10.99 (4.63) µg/dL. Among blood-tested participants included at age 38 years, mean WAIS-IV score was 101.16 (14.82) and mean NZSEI-06 score was 49.75 (17.12). After adjusting for maternal IQ, childhood IQ, and childhood socioeconomic status, each 5-µg/dL higher level of blood lead in childhood was associated with a 1.61-point lower score (95% CI, -2.48 to -0.74) in adult IQ, a 2.07-point lower score (95% CI, -3.14 to -1.01) in perceptual reasoning, and a 1.26-point lower score (95% CI, -2.38 to -0.14) in working memory. Associations of childhood blood lead level with deficits in verbal comprehension and processing speed were not statistically significant. After adjusting for confounders, each 5-µg/dL higher level of blood lead in childhood was associated with a 1.79-unit lower score (95% CI, -3.17 to -0.40) in socioeconomic status. An association between greater blood lead levels and a decline in IQ and socioeconomic status from childhood to adulthood was observed with 40% of the association with downward mobility mediated by cognitive decline from childhood.Conclusions and Relevance: In this cohort born in New Zealand in 1972-1973, childhood lead exposure was associated with lower cognitive function and socioeconomic status at age 38 years and with declines in IQ and with downward social mobility. Childhood lead exposure may have long-term ramifications. [ABSTRACT FROM AUTHOR]

Objectives: Early-life intelligence has been shown to predict multiple causes of death in populations around the world. This finding suggests that intelligence might influence mortality through its effects on a general process of physiological deterioration (i.e., individual variation in "biological age"). We examined whether intelligence could predict measures of aging at midlife before the onset of most age-related disease. Methods: We tested whether intelligence assessed in early childhood, middle childhood, and midlife predicted midlife biological age in members of the Dunedin Study, a population-representative birth cohort. Results: Lower intelligence predicted more advanced biological age at midlife as captured by perceived facial age, a 10-biomarker algorithm based on data from the National Health and Nutrition Examination Survey (NHANES), and Framingham heart age (r = 0.1-0.2). Correlations between intelligence and telomere length were less consistent. The associations between intelligence and biological age were not explained by differences in childhood health or parental socioeco-nomic status, and intelligence remained a significant predictor of biological age even when intelligence was assessed before Study members began their formal schooling. Discussion: These results suggest that accelerated aging may serve as one of the factors linking low early-life intelligence to increased rates of morbidity and mortality. [ABSTRACT FROM AUTHOR]

People exposed to adverse childhood experiences (ACEs) suffer from an increased risk of chronic disease and shorter lifespan. These individuals also tend to exhibit accelerated reproductive development and show signs of advanced cellular aging as early as childhood. These observations suggest that ACEs may accelerate biological processes of aging through direct or indirect mechanisms; however, few population-based studies have data to test this hypothesis. We analysed ACEs and biological aging data from the Canadian Longitudinal Study on Aging (CLSA; n = 23,354 adults aged 45–85) and used the BioAge R package to compute three indices of biological aging from blood-chemistry and organ-function data: Klemera-Doubal method (KDM) biological age, phenotypic age (PA), and homeostatic dysregulation (HD). Adults with ACEs tended to be biologically older than those with no ACEs, although the observed effect-sizes were small (Cohen's d<0.15), with the exception of neglect (d=0.35 for KDM and PA). Associations were similar for men and women and tended to be smaller for older as compared to midlife participants. Subtypes of ACEs perceived as being more severe (e.g., being pushed or kicked, experiencing forced sexual activity, witnessing physical violence) and more frequent and diverse exposures were associated with relatively larger effect-sizes. These findings support the hypothesis that ACEs contribute to accelerated biological aging, although replication is needed in studies with access to prospective records of ACEs and cellular-level measurements of biological aging. Furthermore, future work to better understand the degree to which associations between ACEs and biological aging are moderated by specific life-course pathways, and mediated by lifestyle and socioeconomic factors is warranted. • We studied adverse childhood experiences in 23,354 Canadian older adults. • ACEs are broadly associated with biological aging in adults aged 45–85. • Associations were similar between sexes and smaller for older adults. • Neglect and severe physical and sexual abuse were most strongly associated. [ABSTRACT FROM AUTHOR]