Educational level and characteristics of invasive breast cancer: findings from a French prospective cohort.

PURPOSE: Breast cancer (BC) characteristics are known to influence patients survival. Social differences have been reported by previous studies for those characteristics but questions persist because of inconsistent conclusions. We aimed to investigate the impact of education on BC stage, grade, and hormone receptor (HR) status, while adjusting for potential confounders including a broad set of health behaviors, anthropometric measures, and reproductive factors. METHODS: In the French E3N cohort, 5236 women developed a primary invasive BC for which there was available information on stage, grade, and HR status. No multivariate analyses was performed for BC stage based on the lack of association in bivariate analyses. Odds ratios and confidence intervals were estimated using multinomial logistic regression models for BC grade or binomial logistic regression models for HR status of BC. RESULTS: Women with a lower education were diagnosed with higher grade BC compared to women with a higher education (1.32 [1.12; 1.57]). This association was slightly attenuated after adjustment for covariates independently and more strongly affected in the fully adjusted model (1.20 [0.99; 1.45]). A significant association was observed between lower education and HR- status of BC (1.20 [1.02; 1.42]) attenuated after adjustment for age at first childbirth (1.12 [0.95; 1.33]). CONCLUSION: In this cohort, education was associated with BC grade and HR status but not stage at diagnosis. The link between education and BC grade was not entirely explained by the different adjustments. A specific mechanism could be at play and deserves further investigations.

Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort.

BACKGROUND: Multimorbidity, known as the co-occurrence of at least two chronic conditions, has become of increasing concern in the current context of ageing populations, though it affects all ages. Early life risk factors of multimorbidity include adverse childhood experiences (ACEs), particularly associated with psychological conditions and weight problems. Few studies have considered related mechanisms and focus on old age participants. We are interested in estimating, from young adulthood, the risk of overweight-depression comorbidity related to ACEs while adjusting for early life confounders and intermediate variables. METHODS: We used data from the 1958 National Child Development Study, a prospective birth cohort study (N = 18 558). A four-category outcome (no condition, overweight only, depression only and, overweight-depression comorbidity) was constructed at 23, 33, and 42 years. Multinomial logistic regression models adjusting for intermediate variables co-occurring with this outcome were created. ACEs and sex interaction on comorbidity risk was tested. RESULTS: In our study sample (N = 7762), we found that ACEs were associated with overweight-depression comorbidity risk throughout adulthood (RRR [95% CI] at 23y = 3.80 [2.10-6.88]) though less overtime. Comorbidity risk was larger than risk of separate conditions. Intermediate variables explained part of the association. After full-adjustment, an association remained (RRR [95% CI] at 23y = 2.00 [1.08-3.72]). Comorbidity risk related to ACEs differed by sex at 42. CONCLUSION: Our study provides evidence on the link and potential mechanisms between ACEs and the co-occurrence of mental and physical diseases throughout the life-course. We suggest addressing ACEs in intervention strategies and public policies to go beyond single disease prevention.

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.

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.

Toward a conceptual framework of health and its operational definition: an application in the 1958 British birth cohort.

BACKGROUND: Defining and measuring Health presents a challenge, partly due to its conceptual pluralism. To measure Health as an ability to adapt and self-manage, we developed an approach within the theoretical framework of resources and reserves over the life course, recently proposed in the literature. We aimed to (i) use the conceptual framework developed to identify indicators of deteriorating health reserves, (ii) construct an overall health measure from these indicators, (iii) evaluate the association between the overall health measure and subsequent health outcomes and (iv) assess the robustness of our method. METHODS: We used data from 7,043 individuals born in 1958 in Great Britain included in the National Child Development Study. An overall health measure was constructed via the sum of three selected indicators of deteriorating health reserves in mid-life: chronic widespread pain (CWP), Clinical Interview Schedule - revised (CIS-r), and allostatic load (AL). A three-category variable was defined: impaired/medium/optimal overall health. We explored criterion validity by modelling the relationships between the overall health measure, or each reserve taken separately at 44-45 years, and self-rated health at 46 years and mortality up to 58 years, corresponding to 14 years of follow up, using Cox and logistic regressions respectively. We performed comparative analyses to assess the robustness of the method. RESULTS: Having an impaired overall health measure was significantly associated with all-cause premature mortality (HRimpaired = 2.74 [1.86; 4.05]) and an increased risk of later fair/poor/very poor self-rated health (ORimpaired = 7.50 [6.29; 8.95]). The overall health measure had a greater effect on the self-rated health estimates than each indicator of deteriorating health reserves considered separately (ORAL medium = 1.82 [1.59; 2.09]; ORAL high = 2.74 [2.37; 3.16]; ORCIS-r = 5.20 [4.45; 6.08]; ORCWP = 2.85 [2.53; 3.21]). CIS-r and allostatic load were also associated with premature mortality contrary to chronic widespread pain (HRAL medium1.82 [1.27; 2.61]; HRAL high = 3.10 [2.19; 4.40]; HRCIS-r = 1.77 [1.22; 2.56]; HRCWP = 1.32 [0.98; 1.76]). The multiple comparative analyses conducted allowed us to assess the robustness of our method within this cohort. CONCLUSIONS: We proposed a method for measuring Health in mid-life in line with the concept of Health as the ability to adapt and self-manage and the concept of health reserves. This method may be applied and further developed within the field of social and positive epidemiology.

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]).

Could teacher-perceived parental interest be an important factor in understanding how education relates to later physiological health? A life course approach.

Education is associated with later health, and notably with an indicator of physiological health measuring the cost of adapting to stressful conditions, named allostatic load. Education is itself the result of a number of upstream variables. We examined the origins of educational attainment through the lens of interactions between families and school i.e. parents' interest in their child's education as perceived by teachers. This study aims to examine whether parental interest during a child's educational trajectory is associated with subsequent allostatic load, and whether education or other pathways mediate this relationship. We used data from 9 377 women and men born in 1958 in Great Britain and included in the National Child Development Study to conduct secondary data analyses. Parental interest was measured from questionnaire responses by teachers collected at age 7, 11 and 16. Allostatic load was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Linear regression analyses were carried out on a sample of 8 113 participants with complete data for allostatic load, missing data were imputed. Participants whose parents were considered to be uninterested in their education by their teacher had a higher allostatic load on average in midlife in both men (ß = 0,41 [0,29; 0,54]) and women (ß = 0,69 [0,54; 0,83]). We examined the role of the educational and other pathways including psychosocial, material/financial, and behavioral variables, as potential mediators in the relationship between parental interest and allostatic load. The direct link between parental interest and allostatic load was completely mediated in men, but only partially mediated in women. This work provides evidence that parents' interest in their child's education as perceived by teachers is associated with subsequent physiological health in mid-life and may highlight a form of cultural dissonance between family and educational spheres.

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.

Patterning of educational attainment across inflammatory markers: Findings from a multi-cohort study.

BACKGROUND: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1ß and tumor necrosis factor α- in 6 European cohort studies. METHODS: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation. RESULTS: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1ß and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated with higher inflammation even after adjusting for health behaviours and body mass index. No association was found with interleukin 1ß and tumor necrosis factor α. CONCLUSIONS: Our study suggests different educational patterning of inflammatory biomarkers. Further large-scale research is needed to explore social differences in the inflammatory cascade in greater detail and the extent to which these differences contribute to social inequalities in health.

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.

Education, biological ageing, all-cause and cause-specific mortality and morbidity: UK biobank cohort study.

BACKGROUND: Socioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours. METHODS: Using data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings. FINDINGS: An increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12-1.16] and 1.09 [1.07-1.12] in men and women respectively), cancer (HR = 1.11 [1.09-1.14] and 1.07 [1.04-1.10]) and CVD (HR = 1.25 [1.20-1.31] and 1.21 [1.11-1.31]) mortality, CVD incidence (HR = 1.15 [1.13-1.16] and 1.17 [1.15-1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21-1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours. INTERPRETATION: The BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death.

Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease.

AIMS: To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). METHODS AND RESULTS: We used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10-14 to 1.0 × 10-6 (discovery) and P = 5.6 × 10-10 to 1.1 × 10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05). CONCLUSION: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis.

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.

Multi-cohort study identifies social determinants of systemic inflammation over the life course.

Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.

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.