Project

Discipline

cardio-metabolic disorders; biological mechanisms; lifestyle factors; lifecourse; socioeconomic status; epigenetics; cohort studies

Lead
Numerosi studi mostrano che le malattie cardio-metaboliche sono molto più frequenti nelle fasce più svantaggiate della popolazione. Questo progetto utilizzerà dati provenienti da vari paesi per analizzare i meccanismi biologici (ad esempio epigenetici, infiammatori, etc) che spiegano il legame tra avversità sociale nel corso della vita e insorgenza delle malattie cardio-metaboliche all’età adulta.
Lay summary
Soggetto e obiettivo Le disuguaglianze sociali in salute sono un fenomeno onnipresente. Tuttavia, la ricerca deve ancora fornire una comprensione completa dei meccanismi sottostanti. Studi recenti hanno suggerito che le differenze negli stili di vita possono contribuire a spiegare una grande percentuale delle disuguaglianze sociali in salute. Negli ultimi anni, la ricerca ha iniziato ad affrontare la questione di come lo stato socio-economico sia concretamente incorporato in termini biologici. Questo progetto di ricerca si concentrerà sulle malattie cardio-metaboliche, che mostrano un forte gradiente sociale e il cui onere nelle fasce più svantaggiate della società è in rapido aumento in tutto il mondo. L'obiettivo generale è quello di estendere lo studio delle disuguaglianze sociali in salute e dei loro determinanti, integrando l'analisi dei meccanismi biologici che collegano l’avversità sociale durante tutta la vita e le malattie cardio-metaboliche. Contesto socio-scientifico La multidisciplinarietà (epidemiologia sociale, cardiovascolare, cardio-metabolica e genetica, salute pubblica, medicina del sonno, medicina interna, e biologia molecolare) che caratterizza questo progetto di ricerca offre un potenziale per produrre risposte nuove e innovative alla questione di come lo stato socioeconomico nel corso della vita possa influenzare la salute fino a decenni più tardi. Inoltre, l'uso di cinque basi di dati provenienti da diversi paesi e che offrono un vasto numero di fenotipi misurati ripetutamente nel tempo, insieme ad indicatori precisi dello stato socioeconomico consentirà la replica dei risultati e l'esame delle variazioni potenziali tra paesi.

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Last update: 02.09.2013

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Social inequalities in health are a ubiquitous phenomenon. Conversely, research still has to provide a comprehensive understanding of the mechanisms underlying them. Several processes of social causation have been postulated, including patterns of unhealthy behaviors, psychosocial factors, and living and working conditions. Recent studies suggested that differences in lifestyle may contribute to a large proportion of social inequalities in health. In the last years, research started addressing the issue of how socioeconomic status eventually “gets under the skin”. Human and animal studies have identified several interrelated processes through which the social environment could be embedded, including dysregulation of the hypothalamic-pituitary-adrenal axis, inflammatory processes, neural function and structure, and, ultimately, epigenetic mechanisms. These studies cover a promising new field of research, and several questions remain to be addressed: 1.Studies examining the biology of social adversity have generally described socioeconomic differences in biological markers, but the actual contribution of these intermediate steps to social inequalities in chronic diseases has rarely been evaluated. Further, few studies have evaluated the interactions between lifestyle-related risk factors and biological markers. 2.Some new lifestyle factors potentially implicated in the etiology of socioeconomic differences in health, such as inadequate sleep, have been under-researched. 3.The influence of early life vs. adult socioeconomic status on the biological pathways leading to diseases remains unknown, as well as the extent to which the impact of early life exposure to social adversity can be modified later in life. This research project will focus on cardio-metabolic disorders, which show a strong gradient in their social distribution and whose burden on the most disadvantaged sections of society is rapidly increasing worldwide. The overarching aim is to extend the study of social inequalities in health and their determinants by incorporating an analysis of the biological mechanisms linking lifetime social adversity to cardio-metabolic disease. Specific aims of this research are: 1.To assess the contribution of lifestyle factors (unhealthy behaviors, chronic stress and inadequate sleep) to the association between lifecourse socioeconomic status and cardio-metabolic disorders. 2.To establish the extent to which the contribution of lifestyle factors to social inequalities in cardio-metabolic disorders is mediated by socioeconomic differences in inflammatory markers.3.To understand if social adversity in early life has an impact on gene expression and DNA methylation, and if this can partly explain socioeconomic differences in inflammatory markers. This research project will provide a better understanding of the social, behavioural and biological pathways leading from lifetime socioeconomic adversity to adult life cardio-metabolic disease risk. This will not only add further observations on the role of exposure in early life in shaping health through adulthood, but will also clarify to what extent exposure to early life social adversity has an impact on adult health through behavioural vs. biological pathways. Moreover, this research will establish the extent to which the undesirable health consequences of adverse social exposure in early life are potentially reversible. Last but not least, an epigenome-wide analysis of socioeconomic differences in gene regulation will allow new insight to be gained into the mechanisms through which the social environment has an impact on health. Analyses will be conducted using data from 3 Swiss population-based studies (the CoLaus study, N=6000; the Bus Santé study, N=15,000; the SKIPOGH study, N=1100), the British Whitehall II study (N=10,308), and the multi-country METS study (N=2500). All studies have a longitudinal design allowing the assessment of incident health outcomes. Several indicators of socioeconomic status across the lifecourse (educational level, income, father’s occupation, among others) will be used in this research project. Lifestyle factors considered are health behaviors (smoking, alcohol consumption, diet and physical activity), inadequate sleep and chronic stress. Information on epigenome-wide gene expression and DNA methylation will be collected in a subsample of 250 participants of the SKIPOGH study. The multidisciplinarity (social epidemiology, cardiovascular, cardio-metabolic and genetic epidemiology, public health, sleep medicine, internal medicine, and molecular biology) characterizing this research project offers potential to produce novel and innovative answers to the question of how socioeconomic status over the lifecourse leads to disease decades later. Further, the use of five datasets offering a vast number of phenotypes measured repeatedly over time, along with precise indicators of socioeconomic status over the lifecourse, will allow the replication of results to ensure their consistency and the examination of between-country variations.