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Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

ABSTRACT: Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

SUBMITTER: Carmeli C

PROVIDER: S-EPMC7862626 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

Carmeli Cristian C Kutalik Zoltán Z Mishra Pashupati P PP Porcu Eleonora E Delpierre Cyrille C Delaneau Olivier O Kelly-Irving Michelle M Bochud Murielle M Dhayat Nasser A NA Ponte Belen B Pruijm Menno M Ehret Georg G Kähönen Mika M Lehtimäki Terho T Raitakari Olli T OT Vineis Paolo P Kivimäki Mika M Chadeau-Hyam Marc M Dermitzakis Emmanouil E Vuilleumier Nicolas N Stringhini Silvia S

Scientific reports 20210204 1

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from ...[more]

PMID: 33542415

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Project description:ImportanceThere are consistent data demonstrating that socioeconomic disadvantage is associated with risk of premature mortality, but research on the relationship between neighborhood socioeconomic factors and premature mortality is limited. Most studies evaluating the association between neighborhood socioeconomic status (SES) and mortality have used a single assessment of SES during middle to older adulthood, thereby not considering the contribution of early life neighborhood SES.ObjectiveTo investigate the association of life course neighborhood SES and premature mortality.Design, setting, and participantsThis cohort study included Black and White participants of the multicenter Atherosclerosis Risk in Communities Study, a multicenter study conducted in 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the northwestern suburbs of Minneapolis, Minnesota. Participants were followed up for a mean (SD) of 18.8 (5.7) years (1996-2020). Statistical analysis was performed from March 2023 through May 2024.ExposureParticipants' residential addresses during childhood, young adulthood, and middle adulthood were linked with US Census-based socioeconomic indicators to create summary neighborhood SES scores for each of these life epochs. Neighborhood SES scores were categorized into distribution-based tertiles.Main outcomes and measuresPremature death was defined as all-cause mortality occurring before age 75 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs.ResultsAmong 12 610 study participants, the mean (SD) age at baseline was 62.6 (5.6) years; 3181 (25.2%) were Black and 9429 (74.8%) were White; and 7222 (57.3%) were women. The lowest, compared with the highest tertile, of neighborhood SES score in middle adulthood was associated with higher risk of premature mortality (HR, 1.28; 95% CI, 1.07-1.54). Similar associations were observed for neighborhood SES in young adulthood among women (HR, 1.25; 95% CI, 1.00-1.56) and neighborhood SES in childhood among White participants (HR, 1.25; 95% CI, 1.01-1.56). Participants whose neighborhood SES remained low from young to middle adulthood had an increased premature mortality risk compared with those whose neighborhood SES remained high (HR, 1.25; 95% CI, 1.05-1.49).Conclusions and relevanceIn this study, low neighborhood SES was associated with premature mortality. The risk of premature mortality was greatest among individuals experiencing persistently low neighborhood SES from young to middle adulthood. Place-based interventions that target neighborhood social determinants of health should be designed from a life course perspective that accounts for early-life socioeconomic inequality.

Project description:BackgroundThere is growing recognition of the contribution of the social determinants of health to the burden of many infectious diseases. However, the relationship between socioeconomic status and the incidence and outcome of melioidosis is incompletely defined.MethodsAll residents of Far North Queensland, tropical Australia with culture-proven melioidosis between January 1998 and December 2020 were eligible for the study. Their demographics, comorbidities and socioeconomic status were correlated with their clinical course. Socioeconomic status was determined using the Socio-Economic Indexes for Areas (SEIFA) Index of Relative Socio-economic Disadvantage score, a measure of socioeconomic disadvantage developed by the Australian Bureau of Statistics. Socioeconomic disadvantage was defined as residence in a region with a SEIFA score in the lowest decile in Australia.Results321 eligible individuals were diagnosed with melioidosis during the study period, 174 (54.2%) identified as Indigenous Australians; 223/321 (69.5%) were bacteraemic, 85/321 (26.5%) required Intensive Care Unit (ICU) admission and 37/321 (11.5%) died. 156/321 (48.6%) were socioeconomically disadvantaged, compared with 56603/269002 (21.0%) of the local general population (p<0.001). Socioeconomically disadvantaged patients were younger, more likely to be female, Indigenous, diabetic or have renal disease. They were also more likely to die prior to hospital discharge (26/156 (16.7%) versus 11/165 (6.7%), p = 0.002) and to die at a younger age (median (IQR) age: 50 (38-68) versus 65 (59-81) years, p = 0.02). In multivariate analysis that included age, Indigenous status, the presence of bacteraemia, ICU admission and the year of hospitalisation, only socioeconomic disadvantage (odds ratio (OR) (95% confidence interval (CI)): 2.49 (1.16-5.35), p = 0.02) and ICU admission (OR (95% CI): 4.79 (2.33-9.86), p<0.001) were independently associated with death.ConclusionMelioidosis is disease of socioeconomic disadvantage. A more holistic approach to the delivery of healthcare which addresses the social determinants of health is necessary to reduce the burden of this life-threatening disease.

Project description:ObjectiveThis study aimed to determine the association between adolescent socioeconomic status (father's education and adolescent subjective socioeconomic status) and adult quality of life and the mediation roles of adult socioeconomic status, social capital and lifestyle (physical activity and exposure to smoke) among the "Tehran University of Medical Sciences Employees Cohort (TEC) Study" participants.MethodData of 4455 participants were derived from the Tehran University of Medical Sciences Employees Cohort (TEC) Study. In this study, the World Health Organization quality of life-BREF, the World Bank's Integrated and the International Physical Activity Questionnaire were used. Data were analyzed with structural equation modeling using SPSS Amos 24.0 program.ResultsThe mean age of the participants was 42.31 years (SD: 8.37) and most of the subjects were female (60.7%). Correlation analysis results revealed that, quality of life had a significant and positive association with adolescent subjective socioeconomic status (r = 0.169, p < 0.01) and father's education (r = 0.091, p < 0.01). A mediation model testing the direct relationship between adolescent socioeconomic status and adult socioeconomic status and quality of life, showed a positive relationship between adolescent subjective socioeconomic status (β = 0.229, p < 0.001) and father's education (β = 0.443, p < 0.001) with adult socioeconomic status. Adult socioeconomic status was positively related to quality of life (β = 0.205, p < 0.001). Adult socioeconomic status mediated the relationship between adolescent subjective socioeconomic status (β = 0.047, p < 0.01) and father's education (β = 0.091, p < 0.01) with quality of life. While adult socioeconomic status fully mediated the relationship between the father's education and quality of life, it partially mediated the adolescent subjective socioeconomic status-quality of life association. Other variables such as social capital and lifestyle did not have mediator role in a mediation model.ConclusionThis study provides the evidence for the role of adult socioeconomic status as a partial mediator between adolescent subjective socioeconomic status and quality of life. Therefore, there are several unknown mediators other than adult socioeconomic status that need to be explored in future studies.

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Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

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Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

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