The effect of smoking initiation in adolescence on the subsequent smoking trajectories of people who smoke, and the role of adverse childhood experiences: Results from the 1958 British cohort study.

OBJECTIVE: To examine the association between smoking initiation in adolescence and subsequent different smoking trajectories of people who smoke, and to examine the combined effect of adverse childhood experiences (ACEs) and smoking initiation in adolescence on smoking trajectories of people who smoke. DESIGN AND SAMPLE: Data are from 8757 individuals in Great Britain from the birth cohort National Child Development Study and who reported being smokers or former smokers by age 23. MEASUREMENTS: Smoking initiation in adolescence was measured at 16 y and smoking trajectories were derived from smoking variables from ages 23 to 55. We modelled the relationship between smoking initiation in adolescence with or without ACEs and smoking trajectories. RESULTS: Individuals who initiated smoking in adolescence were more likely to quit later than quitting in twenties (RRR quitting in thirties  = 3.43 [2.40; 4.89] p < .001; RRR quitting in forties  = 5.25 [3.38; 8.14] p < .001; RRR quitting in fifties  = 4.48 [2.95; 6.79] p < .001), to relapse (RRR Relapse  = 3.66 [2.82; 4.76] p < .001) and to be persistent smokers (RRR persistent  = 5.25 [3.81; 7.25] p < .001) compared to those who had initiated smoking in young adulthood. These effects were particularly pronounced in case of ACEs. CONCLUSION: Smoking prevention programs aimed at reducing smoking initiation should be promoted to adolescents to limit the burden of smoking, especially for people who have suffered adversity during childhood.

Educational patterning in biological health seven years apart: Findings from the Tromsø Study.

BACKGROUND: Social-to-biological processes is one set of mechanisms underlying the relationship between social position and health. However, very few studies have focused on the relationship between social factors and biology at multiple time points. This work investigates the relationship between education and the dynamic changes in a composite Biological Health Score (BHS) using two time points seven years apart in a Norwegian adult population. METHODS: We used data from individuals aged 30 years and above who participated in Tromsø6 (2007-2008) and Tromsø7 (2015-2016) (n = 8117). BHS was defined using ten biomarkers measured from blood samples and representing three physiological systems (cardiovascular, metabolic, inflammatory). The higher the BHS, the poorer the health status. FINDINGS: Linear regression models carried out on BHS revealed a strong educational gradient at two distinct time points but also over time. People with lower educational attainment were at higher risk of poor biological health at a given time point (ßlow education Tromsø6=0.30 [95 %-CI=0.18-0.43] and ßlow education Tromsø7=0.30 [95 %-CI=0.17-0.42]). They also presented higher longitudinal BHS compared to people with higher education (ßlow education = 0.89 [95 %-CI=0.56-1.23]). Certain biomarkers related to the cardiovascular system and the metabolic system were strongly socially distributed, even after adjustment for sex, age, health behaviours and body mass index. CONCLUSION: This longitudinal analysis highlights that participants with lower education had their biological health deteriorated to a greater extent over time compared to people with higher education. Our findings provide added evidence of the biological embodiment of social position, particularly with respect to dynamic aspects for which little evidence exists.

Assessing How Social Exposures Are Integrated in Exposome Research: A Scoping Review.

BACKGROUND: Exposome research aims to describe and understand the extent to which all the exposures in human environments may affect our health over the lifetime. However, the way in which humans interact with their environment is socially patterned. Failing to account for social factors in research exploring the exposome may underestimate the magnitude of the effect of exposures or mask inequalities in the distribution of both exposures and outcomes. OBJECTIVES: We aimed to describe the extent to which social factors appear in the exposome literature, the manner in which they are used in empirical analyses and statistical modeling, and the way in which they are considered in the overall scientific approach. METHODS: We conducted a scoping review of the literature using three databases (PubMed, Embase, and Web of Science) up to January 2022. We grouped studies based on the way in which the social variables were used in the analyses and quantified the type and frequency of social variables mentioned in the articles. We also qualitatively described the scientific approach used by authors to integrate social variables. RESULTS: We screened 1,001 records, and 73 studies were included in the analysis. Fifty-five (∼75%) used social variables as exposures or confounders or both, and a wide array of social variables were represented in the articles. Individual-level social variables were more often found, especially education and race/ethnicity, as well as neighborhood-level deprivation indices. Half of the studies used a hypothesis-free approach and the other half, a hypothesis-driven approach. However, in the latter group, of 35 studies, only 8 reported and discussed at least one possible social mechanism underlying the relationship observed between the social variable and the outcome. DISCUSSION: Social factors in exposome research should be considered in a more systematic way, considering their role in structuring both the specific external and the internal exposome. Doing so could help to understand the mechanisms of construction and, potentially, alleviate social inequalities in health and mitigate the emergence of new ones. https://doi.org/10.1289/EHP11015.

Associations of adverse childhood experiences with smoking initiation in adolescence and persistence in adulthood, and the role of the childhood environment: Findings from the 1958 British birth cohort.

Adverse childhood experiences (ACEs) have been identified as a strong determinant of smoking. We aimed to examine the association between ACEs and early smoking initiation and subsequent persistence and the contribution of five pathways including family factors, parental involvement, material living conditions, social activities and conscientiousness. Data are from 7414 individuals born in 1958 in Great Britain included in the National Child Development Study. ACEs were measured at ages 7, 11, and 16. Smoking initiation was derived from smoking variables from ages 16 to 42 and persistent smoking was derived from smoking variables from ages 23 to 42. We modelled the relationship between ACEs and smoking, and further assessed the contribution of each pathway using multinomial logistic regressions. During childhood, 20.9% of respondents experienced one ACE and 6.4% two or more. Those who experienced ACEs had a higher risk of initiating smoking by age 16 and of persistent smoking (RRR initiation by 16y = 1.89 [1.62; 2.20] for one ACE; RRR initiation by 16y = 2.36 [1.81; 3.08] for two or more ACEs, and RRR persistent smoking = 2.07 [1.73; 2.47] for one ACE, RRR persistent smoking = 2.59 [1.92; 3.49] for two or more ACEs). The factors that contributed most to explaining these associations were parental smoking, sibling order and conscientiousness. ACEs remained associated with persistent smoking after further adjusting for young adulthood variables. Smoking prevention measures may need to be tailored when considering adolescents from communities where ACEs are more prevalent to curtail initiation, intensity and persistence. FUNDING: This work was supported by the Institut National du Cancer & the Institut de recherche en santé publique (grant agreement: No. [2019-204]).

The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk.

BACKGROUND: Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators. METHODS: We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data. RESULTS: In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy. CONCLUSIONS: These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms.

A multi-omics approach to investigate the inflammatory response to life course socioeconomic position.

Aim: Inflammation represents a potential pathway through which socioeconomic position (SEP) is biologically embedded. Materials & methods: We analyzed inflammatory biomarkers in response to life course SEP by integrating multi-omics DNA-methylation, gene expression and protein level in 178 European Prospective Investigation into Cancer and Nutrition-Italy participants. Results & conclusion: We identified 61 potential cis acting CpG loci whose methylation levels were associated with gene expression at a Bonferroni correction. We examined the relationships between life course SEP and these 61 cis-acting regulatory methylation sites individually and jointly using several scores. Less-advantaged SEP participants exhibit, later in life, a lower inflammatory methylome score, suggesting an overall increased expression of the corresponding inflammatory genes or proteins, supporting the hypothesis that SEP impacts adult physiology through inflammation.

Health inequalities: Embodied evidence across biological layers.

RATIONALE: Socioeconomic disparities have been documented in major non-communicable diseases and in their risk factors, such as obesity, hypertension, diabetes, smoking, physical inactivity, unhealthful diet and heavy drinking. However, a key research question has remained unanswered: is there a separate biological embodiment of socio-economic conditions underlying health disparities, additional and independent of those risk factors? As lifelong socioeconomic circumstances cannot be randomised, one way forward is the examination of different biological layers of evidence, including molecular changes. METHOD: In this methodological paper we report the association of socio-economic disadvantage with (a) long-term health outcomes, before and after taking risk factors into account; (b) biological intermediaries that increase susceptibility to disease, such as childhood obesity; (c) intermediate circulating biomarkers and omic measurements (transcriptomics, DNA methylation, inflammatory proteins, allostatic load); and (d) immunity. In our Lifepath consortium, these analyses have been performed in several cohort studies, countries and contexts, and at different stages of the life course in up to 1.7 million subjects. The main goal is to test the assumption that each layer (death, functional outcomes, DNA, RNA, proteins, infections) is characterized by different types of bias and confounding, and that consistency across layers reinforces causality assessment. RESULTS: The findings show consistent associations of social disparities with unfavourable health outcomes spanning inflammatory biomarkers, DNA or RNA-based markers, infection, indicators of physical functioning and mortality. Although each of these associations has a different set of confounders, a dose-response relationship is nevertheless consistently observed, thus showing the power of our multi-layered approach. CONCLUSIONS: This new evidence supports biological embodiment of social disadvantage, in addition to the impact of known (mainly behavioural) risk factors for disease.

Early-life inequalities and biological ageing: a multisystem Biological Health Score approach in UnderstandingSociety.

Social position is known to play a role in the quality of ageing, notably through the stimulation/dysregulation of key physiological systems in response to external stresses. Using data from one wave of Understanding Society including 9088 participants, we defined, as an extension of the allostatic load, a synthetic Biological Health Score (BHS) capturing the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). We used 16 established blood-derived biomarkers of these systems to calculate the BHS and explored the relative contribution of socioeconomic position to the BHS and its main components across age groups. We identified a systematic decreasing education-related gradient of the BHS (p<0.001) leading to lower biological risk in participants with longer education. Education-related differences in the BHS were detected early in life, and were not attributable to lifestyle and behavioural factors. We found a consistent contribution of the inflammatory and metabolic systems to the overall score throughout from early adulthood onwards, while the contribution of the other four systems seems to vary across age groups and gender. Our findings highlight the social-to-biological processes ultimately leading to health inequalities, and suggest that such disparities can already be detected in the 20-40 years old age group and cannot be fully explained by lifestyle and behavioural factors. This may define early adulthood social condition as a precursor to accelerated biological ageing and as an important target for public health policies.

Socioeconomic position during pregnancy and DNA methylation signatures at three stages across early life: epigenome-wide association studies in the ALSPAC birth cohort.

BACKGROUND: Socioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexplored. METHODS: Using the data from the ALSPAC birth cohort, we performed epigenome-wide association studies of DNA methylation changes at three life stages (birth, n = 914; childhood at mean age 7.5 years, n = 973; and adolescence at mean age 15.5 years, n = 974), measured using the Illumina HumanMethylation450 Beadchip, in relation to pregnancy SEP indicators (maternal and paternal education and occupation). RESULTS: Across the four early life SEP metrics investigated, only maternal education was associated with methylation levels at birth, and four CpGs mapped to SULF1, GLB1L2 and RPUSD1 genes were identified [false discovery rate (FDR)-corrected P-value <0.05]. No epigenetic signature was found associated with maternal education in child samples, but methylation levels at 20 CpG loci were found significantly associated with maternal education in adolescence. Although no overlap was found between the differentially methylated CpG sites at different ages, we identified two CpG sites at birth and during adolescence which are 219 bp apart in the SULF1 gene that encodes an heparan sulphatase involved in modulation of signalling pathways. Using data from an independent birth cohort, the ENVIRONAGE cohort, we were not able to replicate these findings. CONCLUSIONS: Taken together, our results suggest that parental SEP, and particularly maternal education, may influence the offspring's methylome at birth and adolescence.

[Social environment, biological embedding and social inequalities in health]. / Environnement social, incorporation biologique et inégalités sociales de santé.

The social gradient in health refers to the fact that the higher individuals rise in the social hierarchy, the better is their health. Understanding the construction of this gradient is a major challenge in social epidemiology. An original approach consists in looking at how the different exposures (chemical, physical, behavioural, psychosocial…) associated with the social environment are ultimately expressed at the biological level influencing health positively or negatively, referring to the concept of biological embedding. Data from animal models and life course epidemiology have shed new light on the biological mechanisms potentially at play. Recent discoveries from the field of epigenetics provide a better understanding of how the social environment, especially the early environment, can influence biological functioning over the long term or even over several generations. The work on the biological embedding of the social environment in connection with epigenetics still needs to be very largely consolidated, but could constitute a change of perspective in human biology, particularly by reconsidering the influence of the environment on biological functioning, which is not without consequences in terms of public health interventions.

Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort.

The concept of allostatic load (AL) refers to the idea of a global physiological 'wear and tear' resulting from the adaptation to the environment through the stress response systems over the life span. The link between socioeconomic position (SEP) and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. In order to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including eleven year mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load) reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysis revealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to 5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and young adulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)]. Regarding the ability of each physiological system and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous compared to evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biological embodiment in response to stress which ultimately affects mortality.

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology.

Mediating pathways between parental socio-economic position and allostatic load in mid-life: Findings from the 1958 British birth cohort.

Understanding how human environments affect our health by "getting under the skin" and penetrating the cells, organs and physiological systems of our bodies is a key tenet in public health research. Here, we examine the idea that early life socioeconomic position (SEP) can be biologically embodied, potentially leading to the production of health inequalities across population groups. Allostatic load (AL), a composite measure of overall physiological wear-and-tear, could allow for a better understanding of the potential biological pathways playing a role in the construction of the social gradient in adult health. We investigate the factors mediating the link between two components of parental SEP, maternal education (ME) and parental occupation (PO), and AL at 44 years. Data was used from 7573 members of the 1958 British birth cohort follow-up to age 44. AL was constructed using 14 biomarkers representing four physiological systems. We assessed the contribution of financial/materialist, psychological/psychosocial, educational, and health behaviors/BMI pathways over the life course, in mediating the associations between ME, PO and AL. ME and PO were mediated by three pathways: educational, material/financial, and health behaviors, for both men and women. A better understanding of embodiment processes leading to disease development may contribute to developing adapted public policies aiming to reduce health inequalities.

Life-course socioeconomic status and DNA methylation of genes regulating inflammation.

BACKGROUND: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. METHODS: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. RESULTS: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. CONCLUSIONS: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk.