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Population-based RNA profiling in Add Health finds social disparities in inflammatory and antiviral gene regulation to emerge by young adulthood

Cole, Steven W.; Shanahan, Michael J.; Gaydosh, Lauren; & Harris, Kathleen Mullan. (2020). Population-based RNA profiling in Add Health finds social disparities in inflammatory and antiviral gene regulation to emerge by young adulthood. Proceedings of the National Academy of Sciences.

Cole, Steven W.; Shanahan, Michael J.; Gaydosh, Lauren; & Harris, Kathleen Mullan. (2020). Population-based RNA profiling in Add Health finds social disparities in inflammatory and antiviral gene regulation to emerge by young adulthood. Proceedings of the National Academy of Sciences.

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Health in later life and longevity vary substantially across sociodemographic groups, but the biological mechanisms of these disparities remain poorly understood. We conducted a transcriptome profiling study of inflammatory and antiviral gene activity in a large, nationally representative and ethnically diverse sample of young adults and found that sociodemographic variations in the activity of these molecular pathways emerge by young adulthood—well before they manifest as late-life chronic illness. Inflammation related to biobehavioral factors (BMI, smoking), interferons related to individual characteristics (sex, race/ethnicity), and transcription factor and immune-cell activation showed additional links to social context (family poverty, geographic region). These data suggest that interventions early in life may address the predisease physiological disparities that manifest as late-life health disparities.Health in later life varies significantly by individual demographic characteristics such as age, sex, and race/ethnicity, as well as by social factors including socioeconomic status and geographic region. This study examined whether sociodemographic variations in the immune and inflammatory molecular underpinnings of chronic disease might emerge decades earlier in young adulthood. Using data from 1,069 young adults from the National Longitudinal Study of Adolescent to Adult Health (Add Health)—the largest nationally representative and ethnically diverse sample with peripheral blood transcriptome profiles—we analyzed variation in the expression of genes involved in inflammation and type I interferon (IFN) response as a function of individual demographic factors, sociodemographic conditions, and biobehavioral factors (smoking, drinking, and body mass index). Differential gene expression was most pronounced by sex, race/ethnicity, and body mass index (BMI), but transcriptome correlates were identified for every demographic dimension analyzed. Inflammation-related gene expression showed the most pronounced variation as a function of biobehavioral factors (BMI and smoking) whereas type I IFN-related transcripts varied most strongly as a function of individual demographic characteristics (sex and race/ethnicity). Bioinformatic analyses of transcription factor and immune-cell activation based on transcriptome-wide empirical differences identified additional effects of family poverty and geographic region. These results identify pervasive sociodemographic differences in immune-cell gene regulation that emerge by young adulthood and may help explain social disparities in the development of chronic illness and premature mortality at older ages.


Add health
biodemography
life-span developement
social epidemiology
social genomics


JOUR



Cole, Steven W.
Shanahan, Michael J.
Gaydosh, Lauren
Harris, Kathleen Mullan



2020


Proceedings of the National Academy of Sciences










10.1073/pnas.1821367117



8994