Early Life Socioeconomic Position Research Articles

The associations of socioeconomic position with structural brain damage and connectivity and cognitive functioning: The Maastricht Study

BackgroundSocioeconomic inequalities in cognitive impairment may partly act through structural brain damage and reduced connectivity. This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive functioning is mediated by later-life SEP, and whether the associations of SEP with later-life cognitive functioning can be explained by structural brain damage and connectivity. MethodsWe used cross-sectional data from the Dutch population-based Maastricht Study (n = 4,839; mean age 59.2 ± 8.7 years, 49.8% women). Early-life SEP was assessed by self-reported poverty during childhood and parental education. Later-life SEP included education, occupation, and current household income. Participants underwent cognitive testing and 3-T magnetic resonance imaging to measure volumes of white matter hyperintensities, grey matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SEP, markers of structural brain damage and connectivity, and cognitive functioning. Mediation was tested using structural equation modeling. ResultsAlthough there were direct associations between both indicators of SEP and later-life cognitive functioning, a large part of the association between early-life SEP and later-life cognitive functioning was explained by later-life SEP (72.2%). The extent to which structural brain damage or connectivity acted as mediators between SEP and cognitive functioning was small (up to 5.9%). ConclusionsWe observed substantial SEP differences in later-life cognitive functioning. Associations of structural brain damage and connectivity with cognitive functioning were relatively small, and only marginally explained the SEP gradients in cognitive functioning.

Abstract 01: Childhood Socioeconomic Position is Associated With Accelerated Brain Aging in U.S Hispanic/Latino Population. Findings From the Hispanic Community Health Study/Study of Latinos

Introduction: Low childhood socioeconomic position (SEP) may have a long-lasting influence on functional and structural brain development. However, little is known about whether early-life SEP is associated with a steeper age-related reduction in measures of brain structure, previously linked to Alzheimer’s Disease and Related Dementias (ADRD) vulnerability. Hypothesis: Low childhood SEP measured by parental education modifies the association between age and magnetic resonance imaging (MRI)-derived brain volumes, with worse age-related brain volumes among adults with low early-life SEP. Methods: We used data from adults (age range 50-85) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL-INCA-MRI), a population-based cohort study conducted in four major U.S cities. Measures of brain structure (e.g., total brain volume-TBV, total gray matter volume-TGMV, total cortical gray volume-TCGV, hippocampus volume-HV, and white matter hyperintensity volume-WMHV were quantified using MRI in 2400 adults with normal and impaired cognitive function. We used participants' self-reports of the highest education attained by either their father or mother as a proxy for childhood SEP (< high school and ≥ high school). We conducted survey linear regression models of age on brain volumes adjusting for participant’s sex, Hispanic/Latino background, field center, nativity, and age at immigration. We then included interaction terms between age and childhood SEP. Results: In multivariable regression models, older age was associated with smaller brain volumes (β, and 95% confidence interval-CI for TBV for each year increment in age: -3.22, 95% CI: -3.73, -2.71), while older age was associated with larger log-transformed WMHV (β: 0.90, 95% CI: 0.08, 0.10). Childhood SEP modifies the association between age and brain volumes, with significant smaller age-related brain volumes among adults whose parents have less than high school (β for TBV:-3.65, 95% CI: -4.25, -3.04; and TGMV: -1.29, 95% CI: -1.62, -0.95) as compared with those with high school or more (β for TBV: -2.32, 95% CI: -3.17, -1.45; p-value for interaction: 0.024; and TGMV: -0.54, 95% CI: -0.98, -0.10; p-value for interaction: 0.017). These smaller age-related volumes persisted after accounting for participant’s education and income. In contrast, higher childhood SEP was associated with a slightly larger age-related WMHV (β for interaction term: 0.03, 95% CI: 0.01, 0.05, p-value: 0.016). Conclusions: This study highlights the unique contributions of childhood SEP to accelerated brain aging. The age by childhood SEP interaction suggests that childhood socioeconomic disadvantage has a long-lasting influence in accelerated disparities in brain aging as indexed by bran MRI.

THE ASSOCIATIONS OF SOCIOECONOMIC POSITION WITH STRUCTURAL BRAIN DAMAGE AND CONNECTIVITY AND COGNITION

Abstract Socioeconomic inequalities in the risk for cognitive impairment have been reported, which might partly act through structural brain damage and connectivity. This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive performance is mediated by later-life SEP, and whether the association of SEP with later-life cognitive performance can be explained by structural brain damage and connectivity. We used cross-sectional data from the population-based Maastricht study (n=4,839; mean age 59.2±8.7 years, 49.8% women). Early-life SEP was assessed retrospectively by self-reported poverty and parental education. Later-life SEP included education, occupation, and household income. Participants underwent cognitive testing and 3 T magnetic resonance imaging to measure volumes of white matter hyperintensities, gray matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SEP, MRI brain markers and cognition. Structural equation modeling tested mediation. Results indicated that higher SEP was associated with higher grey matter volume, lower white matter volume, and higher structural connectivity. Structural brain damage and lower structural connectivity were associated with lower cognition. Both higher early-life and later-life SEP were associated with higher cognition. The association of early-life SEP with later-life cognition was partly mediated by later-life SES (73.8%). However, the extent to which the association of SEP with cognition could be explained by structural brain damage or connectivity was marginal (up to 5.9%). More research is needed to investigate alternative pathways that can explain the associations between SEP with later-life cognition.

EARLY-LIFE SOCIOECONOMIC POSITION AND LATER-LIFE COGNITIVE FUNCTIONING: A META-ANALYSIS

Abstract A life course perspective on cognitive aging suggests that experiences early in life may be linked to later performance on cognitive tests. A growing literature shows that childhood socioeconomic position (SEP) is positively associated with later-life cognitive functioning. To identify the strength of this association and potential moderating variables, we used meta-analytic techniques to identify the magnitude of the association between early-life (aged 0-17) SEP and later-life (aged 50+) cognitive functioning. After systematically searching PsycINFO, Scopus, and ScienceDirect, 30 studies representing 39 samples and 223,381 participants met the inclusion criteria. Extracted data included participant and study design characteristics, construct operationalization and measures, and effect sizes. The results of the meta-analysis revealed a significant correlation between childhood SEP and later-life cognitive functioning, whether measured as an overall effect size (r = .179, 95% CI = [.156, .201]), global performance (r = .206, 95% CI = [.157, .255]), verbal episodic memory (r = .160, 95% CI = [.132, .188]), verbal fluency (r = .203, 95% CI = [.168, .237]), or processing speed (r = .146 (95% CI = .108, .184]), but not inhibition (r = .146, 95% CI = [-.150, .418]). Subgroup analyses revealed that, in some domains, the correlation was weaker with an older mean sample age. Correlations did not vary by study design (i.e., prospective or retrospective) or journal impact factor. These results provide important evidence for the promotion of policies that buffer children from economic hardship, as one’s cognitive performance in later life begins far earlier than older adulthood.

Early life socioeconomic position contributes to adult obesity independent of adult socioeconomic factors: Findings from The Sister Study cohort

Low socioeconomic position (SEP) has been associated with obesity within life stages; however, life course SEP may also alter downstream obesity risk. Research is needed to understand the impact of childhood SEP, independent of adult SEP, as well as SEP trajectories over the life course on adult obesity risk. We use data from the Sister Study, a prospective U.S. cohort of women aged 35–74 years (N = 50,884; enrollment: 2003–2009). Relative risks (RR) for adult obesity associated with childhood SEP (latent variable) and five latent life course SEP profiles were estimated in overall and race and ethnicity-stratified log binomial regression models. We estimated the direct effect of childhood SEP on adult obesity and mediation by adult SEP. Lower childhood SEP was associated with greater obesity risk (RR = 1.16, 95% CI: 1.15–1.17). In stratified models, RRs were elevated across groups though lower for Black and Hispanic/Latina participants, despite greater prevalence of obesity among Black participants. The direct effect of childhood SEP on adult obesity persisted in mediation models independent of adult SEP (RR = 1.10, 95% CI: 1.08–1.12) with adult SEP mediating approximately 40% of the total effect of childhood SEP on adult obesity. Furthermore, adult obesity risk was elevated for all life course SEP profiles compared to persistent high advantage. Life course SEP profiles indicating greater advantage in adulthood than childhood were not associated with reduced adult obesity risk among those experiencing less than high advantage in childhood. In conclusion, lower childhood SEP, independent of adult SEP, may be an important risk factor for adult obesity.

Early life factors and grip strength at older ages in two distinct populations in China and England

Abstract Background Early life factors are associated with poor physical and mental outcomes in late life. However how these are associated with grip strength, an objective measure of physical capacity and therefore morbidity and mortality in late life unclear. This analysis therefor explores the long-term effects of adverse childhood socioeconomic experiences and health on grip strength in late life, and how these are mediated by adult factors. Methods Data on early life events, health and socioeconomic factors and grip strength were collected from the China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA). Participants’ first entry into the survey from waves 1-3 in CHARLS and waves 1-9 in ELSA were included in the analysis. Sex stratified linear regression models were used to explore how early life factors affect grip strength. Childhood events included parental socioeconomic position and childhood health. Results 17,205 participants from CHARLS and 6,692 participants from ELSA were included in this analysis. Unlike ELSA, participants from CHARLS were younger, had lower education, low-income occupation and obese. Low parental education and poor child health perception were negatively associated with grip strength even after controlling for childhood and adult factors (adult socioeconomic position, adult body size, adult health and lifestyle) in men from both studies. While parental occupation was associated with grip strength for both males and females in both studies. Association of SEP and health in childhood with grip strengths at older ages were however explained by body size and adult health factors, and not adult SEP. Key messages • Early life socioeconomic position has a persistent effect of late physical health, even after considering adult health, socioeconomic position and lifestyle. • Early intervention in socioeconomic inequalities might improve health outcomes across the life course.

Women's Economic Mobility and Small for Gestational Age Rates: The Effect of Paternal Early-Life Socioeconomic Position.

To determine whether paternal early-life socioeconomic position (defined by neighborhood income) modifies the association of maternal economic mobility and infant small for gestational age (weight for gestational age < 10th percentile, SGA) rates. Stratified and multilevel binomial regression analyses were executed on the Illinois transgenerational dataset of parents (born 1956-1976) and their infants (born 1989-1991) with appended U.S. census income information. Only Chicago-born women with an early-life residence in impoverished or affluent neighborhoods were studied. The incidence of impoverished-born women's upward economic mobility among births (n = 3777) with early-life low socioeconomic position (SEP) fathers was less than that of those (n = 576) with early-life high SEP fathers: 56% vs 71%, respectively, p < 0.01. The incidence of affluent-born women's downward economic mobility among births (n = 2370) with early-life low SEP fathers exceeded that of those (n = 3822) with early-life high SEP fathers: 79% vs 66%, respectively, p < 0.01. The adjusted RR of infant SGA for maternal upward (compared to lifelong impoverishment) economic mobility among fathers with early-life low and high SEP equaled 0.68 (0.56, 0.82) and 0.81 (0.47, 1.42), respectively. The adjusted RR of infant SGA for maternal downward (compared to lifelong residence in affluent neighborhoods) economic mobility among fathers with early-life low and high SEP were 1.37 (0.91, 2.05) and 1.17 (0.86, 1.59), respectively. Paternal early-life SEP is associated with maternal economic mobility (both upward and downward); however, it does not modify the relationship between maternal economic mobility and infant SGA rates.

The relationship of childhood adversity with diurnal cortisol patterns and C-reactive protein at 60–64 years of age in the 1946 National Survey of Health and Development

BackgroundEarly life adversity is increasingly prevalent and associated with greater morbidity and mortality. It is hypothesised that the link between psychosocial early life adversity and poor health in adulthood is due to abnormal hypothalamic-pituitary-adrenal (HPA) axis functioning (often measured as cortisol patterning) and inflammation (often measured via c-reactive protein (CRP)). This study aimed to investigate the relationship between early life psychosocial adversity and cortisol patterning and CRP at 60–64 years of age. MethodsThe MRC National Survey of Health and Development (NSHD) was used. The analytic “cortisol sample” included 843 individuals and the “CRP sample” included 1150 individuals. Data on adversity experienced between ages 0–15 years were utilised to compose a cumulative childhood psychosocial early life adversity (ELA) score (0, 1, 2, 3+). CRP and salivary cortisol (waking, 30 min after waking, and evening) were collected at 60–64 years. Associations between the psychosocial ELA score and cortisol outcomes (cortisol awakening response (CAR), diurnal slope (DS), and evening and morning cortisol) were assessed using general linear regression. Tobit regression was used to assess the association between psychosocial ELA score and CRP. Adjustments were made for age at follow-up, sex, childhood maternal education, childhood paternal social class, childhood housing tenure, and birth weight. After testing for sex by ELA score interactions, analyses were repeated stratified by sex for the CRP sample. ResultsIn fully adjusted models, individuals who experienced the highest level of childhood psychosocial adversity (3+) had a 24.63 (−41.49, −7.76) % lower waking cortisol and a 7.30 (1.49, 13.12) % lower decline in cortisol across the day compared to those with a psychosocial ELA score of zero. In females, the highest level of childhood psychosocial adversity, compared to the lowest, was associated with 32.61 (2.98, 62.25) % higher CRP at 60–64 years, which attenuated to 20.38% (−9.38, 50.14) upon adjustment for measures of early life socioeconomic position. Conversely, the association between childhood psychosocial adversity and CRP in males was null. ConclusionsOur results suggest that high-levels of psychosocial adversity in childhood might result in a lower morning cortisol and flatter DS in mid-to-late-adulthood. The finding that adversity was related to higher CRP in females but not males requires replication and further investigation.

International differences in interspousal health correlations

Using objective measures of lung function, we document strong positive associations in health within couples in all European countries but large and significant differences in this correlation within broad European regions, with Southern Europe having by far stronger correlations than elsewhere. We analyze potential explanations for such differences, investigating the role of measures capturing current and past health behaviors, early life circumstances of each spouse, and measures capturing assortative mating in multiple dimensions. We show that marital sorting patterns by dimensions of early life health and socioeconomic position, as well as by geographical subregion within countries, are key to understanding the empirical patterns observed.

Influence of childhood socioeconomic position and ability on mid-life cognitive function: evidence from three British birth cohorts

BackgroundChildhood socioeconomic position (SEP) is robustly associated with cognitive function later in life. However, it is unclear whether this reflects a direct relationship, or an indirect association via modifiable factors...

Early-Life Socioeconomic Position and the Accumulation of Health-Related Deficits by Midlife in the 1958 British Birth Cohort Study.

Reducing population levels of frailty is an important goal, and preventing its development in midadulthood could be pivotal. There is limited evidence on associations between childhood socioeconomic position (SEP) and frailty. Using data on the 1958 British birth cohort (followed from 1958 to 2016; n = 8,711), we aimed to 1) establish the utility of measuring frailty in midlife, by examining associations between a 34-item frailty index at age 50 years (FI50y) and mortality at ages 50–58 years, and 2) examine associations between early-life SEP and FI50y and investigate whether these associations were explained by adult SEP. Hazard ratios for mortality increased with increasing frailty; for example, the sex-adjusted hazard ratio for the highest quintile of FI50y versus the lowest was 4.07 (95% confidence interval (CI): 2.64, 6.25). Lower early-life SEP was associated with higher FI50y. Compared with participants born in the highest social class, the estimated total effect on FI50y was 42.0% (95% CI: 35.5, 48.4) for participants born in the lowest class, with the proportion mediated by adult SEP being 0.45% (95% CI: 0.35, 0.55). Mediation by adult SEP was negligible for other early-life SEP classes. Findings suggest that early-life SEP is associated with frailty and that adult SEP only partially explains this association. Results highlight the importance of improving socioeconomic circumstances across the life course to reduce inequalities in midlife frailty.

Socioeconomic inequalities in blood pressure: co-ordinated analysis of 147,775 participants from repeated birth cohort and cross-sectional datasets, 1989 to 2016

BackgroundHigh blood pressure (BP) is a key modifiable determinant of cardiovascular disease and a likely determinant of other adverse health outcomes. While socioeconomic inequalities in BP are well documented, it remains unclear (1) how these inequalities have changed across time, given improvements over time in the detection and treatment of high BP (hypertension); (2) whether BP inequalities are present below and above hypertension treatment thresholds; and (3) whether socioeconomic position (SEP) across life has cumulative effects on BP. We sought to address these gaps using evidence from two complementary sources: birth cohort and repeated cross-sectional datasets.MethodsWe used three British birth cohort studies—born in 1946, 1958, and 1970—with BP measured at 43–46 years (in 1989, 2003, and 2016), and 21 repeated cross-sectional datasets—the Health Survey for England (HSE), with BP measured among adults aged ≥ 25 years (1994–2016). Adult education attainment was used as an indicator of SEP in both datasets; childhood father’s social class was used as an alternative indicator of (early life) SEP in cohorts. Adjusting for the expected average effects of antihypertensive medication use, we used linear regression to quantify SEP differences in mean systolic BP (SBP), and quantile regression to investigate whether inequalities differed across SBP distributions—below and above hypertension treatment thresholds.ResultsIn both datasets, lower educational attainment was associated with higher SBP, with similar absolute magnitudes of inequality across the studied period. Differences in SBP by education (Slope Index of Inequality) based on HSE data were 3.0 mmHg (95% CI 1.8, 4.2) in 1994 and 4.3 mmHg (2.3, 6.3) in 2016. Findings were similar for diastolic BP (DBP) and survey-defined hypertension. Inequalities were found across the SBP distribution in both datasets—below and above the hypertension threshold—yet were larger at the upper tail; in HSE, median SBP differences were 2.8 mmHg (1.7, 3.9) yet 5.6 mmHg (4.9, 6.4) at the 90th quantile. Adjustment for antihypertensive medication use had little impact on the magnitude of inequalities; in contrast, associations were largely attenuated after adjustment for body mass index. Finally, cohort data suggested that disadvantage in early and adult life had cumulative independent associations with BP: cohort-pooled differences in SBP were 5.0 mmHg (3.8, 6.1) in a score combining early life social class and own education, yet were 3.4 mmHg (2.4, 4.4) for education alone.ConclusionSocioeconomic inequalities in BP have persisted from 1989 to 2016 in Britain/England, despite improved detection and treatment of high BP. To achieve future reductions in BP inequalities, policies addressing the wider structural determinants of high BP levels are likely required, particularly those curtailing the obesogenic environment—targeting detection and treatment alone is unlikely to be sufficient.

Fertility History and Biomarkers Using Prospective Data: Evidence From the 1958 National Child Development Study

Research on the later-life health implications of fertility history has predominantly considered associations with mortality or self-reported indicators of health. Most of this previous research has either not been able to account for selection factors related to both early-life and later-life health or has had to rely on retrospectively reported accounts of childhood circumstances. Using the 1958 National Child Development Study, and in particular the biomedical survey conducted in 2002–2003, we investigate associations between fertility histories (number of children and age at first and at last birth) and biomarkers for cardiometabolic risk and respiratory function in midlife among both men and women. Results from models that adjusted for a very wide range of childhood factors, including early-life socioeconomic position, cognitive ability, and mental health, showed weak associations between parity and biomarkers. However, we found an inverse association between age at first birth and biomarkers indicative of worse cardiometabolic health, with poorer outcomes for those with very young ages at entry to parenthood and increasingly better outcomes for those becoming parents at older ages. A very young age at last birth was also associated with less favorable biomarker levels, especially among women. Results highlight the value of prospectively collected data and the availability of biomarkers in studies of life course determinants of health in midlife and later.

Measuring Child Socio-Economic Position in Birth Cohort Research: The Development of a Novel Standardized Household Income Indicator.

The assessment of early life socioeconomic position (SEP) is essential to the tackling of social inequalities in health. Although different indicators capture different SEP dimensions, maternal education is often used as the only indicator in birth cohort research, especially in multi-cohort analyses. Household income, as a direct measure of material resources, is one of the most important indicators, but one that is underused because it is difficult to measure through questionnaires. We propose a method to construct a standardized, cross-cohort comparable income indicator, the “Equivalized Household Income Indicator (EHII)”, which measures the equivalized disposable household income, using external data from the pan-European Union Statistics on Income and Living Conditions (EUSILC) surveys, and data from the cohorts. We apply this method to four studies, Piccolipiù and NINFEA from Italy and ELFE and EDEN from France, comparing the distribution of EHII with other SEP-related variables available in the cohorts, and estimating the association between EHII and child body mass index (BMI). We found that basic parental and household characteristics may be used, with a fairly good performance, to predict the household income. We observed a strong correlation between EHII and both the self-reported income, whenever available, and other individual socioeconomic-related variables, and an inverse association with child BMI. EHII could contribute to improving research on social inequalities in health, in particular in the context of European birth cohort collaborative studies.

Early-life social and health determinants of adult socioeconomic position: associations and trends across generations

BackgroundSocial and biological circumstances at birth are established predictors of adult socioeconomic position (SEP). This study aims to assess the trends in these associations across two generations and examine the...

EARLY-LIFE SOCIOECONOMIC POSITION AND ACCUMULATION OF HEALTH-RELATED DEFICITS IN MIDLIFE

Improved understanding of predictors of frailty is key to delaying its onset. Yet, few studies have examined whether early-life socioeconomic position (SEP) predicts frailty in midlife. In the 1958 British Birth Cohort (n=7601), we examined (i) associations between early-life SEP and frailty at 50y and (ii) whether associations were due to continuities in disadvantage into mid-adulthood. Frailty was measured using an index composed of 37 health-deficits. Associations between early-life SEP and frailty were examined using linear regression. Lower early-life SEP was associated with higher frailty, e.g. compared to professional/managerial class, the frailty index was higher by 3.09% (95% CI:-0.65%, 6.84%) for skilled non-manual, 10.8% (8.20%, 13.4%) for skilled manual and 14.2% (11.1%, 17.2%) for partly skilled/unskilled. After adjustment for adult disadvantage, the trend remained, albeit weaker. Findings suggest that interventions in mid-adulthood targeted to those exposed to early-life disadvantage could reduce the risk of developing frailty when entering later life.

INEQUALITIES IN FRAILTY BY SOCIO-ECONOMIC POSITION: IT’S ALL IN THE TIMING

A number of studies have found that higher socio-economic position (SEP) appears protective of becoming frail. However, not only can SEP be defined in early, mid or late life, by education, occupational status or income/material disadvantage respectively, but frailty may occur in the young old as well as the very old. Do the same measures of SEP reflect inequalities in frailty in the young old as the very old? Does it matter when in the lifecourse SEP is measured? Have inequalities in frailty between SEP groups changed across the generations of older people? We seek to answer such questions from cohorts across the spectrum of later life. The first presentation, from the 1958 British Birth Cohort Study, examines the association between early-life SEP and frailty at age 50 and whether this association is due to continued disadvantage into mid-life. The second presentation moves to very old age, examining the role of early, mid and late life disadvantage on the progression of frailty between ages 85 and 90 in the Newcastle 85+ cohort. The third presentation, based on the electronic health records of adults aged 75 years and over in England, focuses on whether SEP modifies frailty trajectories in the last year of life. The final presentation examines whether SEP inequalities in frailty have changed over different generations of older people, and utilises data from the Cognitive Function and Ageing Studies. Together these presentations increase understanding of which SEP groups should be targeted for interventions to reduce frailty throughout later life.

Early life socioeconomic position and adult systemic inflammation: the role of gene regulation

Abstract Background Adverse socioeconomic conditions in childhood affect systemic low-grade inflammation in adulthood. Studies in animals and humans suggest that socioeconomic conditions get under the skin from early life thus contributing to shape pro-inflammatory phenotypes. Although the existence of socioeconomic differences in gene regulation of the immune function have been described previously, no study has so far assessed the extent to which these differences actually explain socioeconomic variations in inflammatory markers. Methods First, we ran 2-sample Mendelian Randomization (MR) methods to identify putative genes whose expression drives C-reactive protein (CRP) levels in blood. We used two databases with summary statistics of associations between single nucleotide polymorphisms and gene expression (eQTLGen, N = 31,486 individuals) and CRP (CHARGE, N = 148,164 individuals) in blood. We tested 10,701 genes and retained those with FDR&amp;lt;0.05. Second, we used individual-participant data from a Swiss population-based study (SKIPOGH, N = 723) to estimate the proportion of the effect of paternal occupational position (SEP) on low-grade inflammation in adulthood (CRP&amp;gt;3mg/L) mediated by the selected genes. We estimated odds ratios and mediated proportions through counterfactual-based mediation models. Results We identified 426 genes driving CRP levels (robust to unmeasured confounding thanks to MR). They jointly mediated the effect of low father’s occupation on inflammation in adulthood for a proportion up to about 70% [95% confidence intervals (CI) 11-90%] and with an odds ratio of 1.53 [95% CI 1.05-2.15] compared to individuals with high paternal SEP. Analysis of the effects of life-course SEP trajectories (upward, downward and stable low from paternal to adult SEP) on gene regulation revealed trajectory dependent effects. Conclusions We suggest that adverse childhood SEP affects systemic inflammation in adulthood through a long-lasting effect on gene regulation.

Lifecourse epidemiology matures: Commentary on Zhang et al. “Early-life socioeconomic status, adolescent cognitive ability, and cognition in late midlife”

The effect of education on late life cognition has attracted substantial attention in lifecourse epidemiology, in part because of its relevance for understanding the effect of education on dementia. Although numerous studies document an association between education and later life cognition, these studies are potentially confounded by early life socioeconomic position and cognition. Good measures of these early life constructs are rarely available in data sets assessing cognition in late life. A further body of evidence has taken advantage of compulsory schooling law (CSL) instrumental variables (IV), although these estimates have been criticized based on questions about the validity of CSL IVs. In this issue of the Journal, Zhang et al. took advantage of the Wisconsin Longitudinal Study to control for both prospectively measured adolescent IQ and early life socioeconomic status in an analysis evaluating the effect of education on cognitive scores in late middle age (Zhang et al., 2019; IN THIS ISSUE). Their results indicate a moderate effect of each additional year of education on later life cognition, of approximately 0.1–0.15 standard deviations per year of schooling. These estimates are remarkably aligned with findings from prior observational designs and from the CSL IV studies. Although criticisms of any individual study are plausible, this new study complements the body of prior evidence to provide compelling evidence for the benefits of education on late life cognition.

Socio-economic position across the lifecourse and risk of breast cancer: findings from EPIC-Italy

Abstract Backgrounds Socio-economic position (SEP) is linked to many health outcomes but the link between SEP and breast cancer (BC) is complex. This study explores the relationship between SEP from early life and future risk of BC. Methods We used data from the Italian component of the European prospective investigation into cancer and nutrition: EPIC-Italy (up to 26,391 women). Cox proportional hazard models were used to estimate the association between measures of life course SEP (father’s occupation, educational level, highest household occupation) with risk of BC, adjusting for health behaviours (smoking, alcohol, physical activity, Mediterranean diet), height, weight and reproductive factors (postmenopausal status, age at first full term pregnancy). To mimic life course experiences, we analysed the relationship between father’s occupation and risk of BC, sequentially adjusting for SEP in young adulthood and adulthood, as well as the impact of social mobility. Results We observed a significant association between father’s occupation and risk of BC, where participant with low SEP had lower risk to develop BC (HR[95%CI] = 0.88[0.78; 0.99]). This association was borderline significant when we analysed educational level and highest household occupation. These associations were only slightly modified after adjustment for health behaviours, height and weight but more strongly affected by reproductive factors. However, the association between father’s occupation and BC remained borderline significant in the fully adjusted model (HR[95%CI] = 0.91[0.80; 1.03]). Stable low trajectory showed a lower risk of BC (HR[95%CI] = 0.82[0.71; 0.96]) slightly attenuated after adjusted for reproductive factors (HR[95%CI] = 0.88 [0.75; 1.03]). Conclusions Our findings suggest that low early-life SEP and stable low trajectory are associated with a lower risk of BC, which is partly explained by reproductive factors. Key messages Low early life socioeconomic position and stable low trajectory are associated with a lower risk of BC. Reproductive factors, especially age at the first full term pregnancy, explain part of these associations.