Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: The multi-ethnic study of atherosclerosis

Needham, Belinda L.; Smith, Jennifer A.; Zhao, Wei; Wang, Xu; Mukherjee, Bhramar; Kardia, Sharon L.R.; Shively, Carol A.; Seeman, Teresa E.; Liu, Yongmei; Roux, Ava V. Diez

doi:10.1080/15592294.2015.1085139

Cited by 164 publications

(152 citation statements)

References 61 publications

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“…EGR4 is a protein coding gene and transcription factor that regulates cell proliferation and proinflammatory cytokine production. These results are consistent with several studies documenting associations between early life socioeconomic status and DNAm in adulthood, drawing on samples from the United States, United Kingdom, Canada, and Italy (30,(47)(48)(49), and with a recent study in the United States showing that higher levels of stress in infancy/early childhood are biologically embedded in the epigenome (27). Our study reports associations between early adversity and DNAm in adulthood in a non-Western, lower income setting.…”

Section: Discussionsupporting

confidence: 92%

“…Target genes were identified using a web-based gene network and functional annotation tool (genemania.org/) and review of prior human studies investigating the genetic and epigenetic control of inflammation (30,48,(67)(68)(69)(70) (additional details on target gene selection are provided in SI Materials and Methods). A total of 249 target genes were identified.…”

Section: Methodsmentioning

confidence: 99%

“…The potential biological relevance of these processes is underscored by several studies documenting associations between DNAm and expression of genes involved in the regulation of inflammation as well as biomarkers of inflammation and risk for inflammation-related disorders (30,32,33).…”

Section: Significancementioning

confidence: 99%

“…Indeed, recent human studies suggest that socioeconomic and psychosocial environments in infancy and childhood leave a molecular imprint that has lasting effects on genomic regulation and the developing phenotype (27)(28)(29)(30). Of the many marks contributing to the epigenome, DNA methylation (DNAm) has been the major focus of human research and involves the covalent linkage of methyl groups to cytosine residues primarily in the context of CpG dinucleotides.…”

mentioning

confidence: 99%

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Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood

McDade

Ryan

Jones

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

105

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Chronic inflammation contributes to a wide range of human diseases, and environments in infancy and childhood are important determinants of inflammatory phenotypes. The underlying biological mechanisms connecting early environments with the regulation of inflammation in adulthood are not known, but epigenetic processes are plausible candidates. We tested the hypothesis that patterns of DNA methylation (DNAm) in inflammatory genes in young adulthood would be predicted by early life nutritional, microbial, and psychosocial exposures previously associated with levels of inflammation. Data come from a population-based longitudinal birth cohort study in metropolitan Cebu, the Philippines, and DNAm was characterized in whole blood samples from 494 participants (age 20–22 y). Analyses focused on probes in 114 target genes involved in the regulation of inflammation, and we identified 10 sites across nine genes where the level of DNAm was significantly predicted by the following variables: household socioeconomic status in childhood, extended absence of a parent in childhood, exposure to animal feces in infancy, birth in the dry season, or duration of exclusive breastfeeding. To evaluate the biological significance of these sites, we tested for associations with a panel of inflammatory biomarkers measured in plasma obtained at the same age as DNAm assessment. Three sites predicted elevated inflammation, and one site predicted lower inflammation, consistent with the interpretation that levels of DNAm at these sites are functionally relevant. This pattern of results points toward DNAm as a potentially important biological mechanism through which developmental environments shape inflammatory phenotypes across the life course.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

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Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood

McDade

Ryan

Jones

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

105

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“…Epigenetic changes in DNA methylation (DNAm) can give rise to heritable changes in gene expression (24). Indeed, DNAm can change across the lifespan, providing a molecular mechanism through which social and behavioral factors are translated into health outcomes (24).…”

Section: Dna Methylation (Dnam)mentioning

confidence: 99%

Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging

Kiecolt‐Glaser

Wilson²

2016

Psychosom Med

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A recent meta-analysis published in Psychosomatic Medicine provides convincing evidence that certain psychiatric populations have shorter telomeres than nonpsychiatric controls, in accord with the strong evidence linking psychiatric disorders with premature mortality. After addressing the clinical significance of shorter telomeres, this editorial describes mechanistic pathways that lead to telomere shortening. Additionally, two other novel methods for measuring biological markers of accelerated aging are briefly discussed, DNA methylation and cellular senescence based on p16INK4a; these innovative approaches could be used to confirm and extend our understanding of psychiatric patients’ increased health and mortality risks.

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Racial and Ethnic Residential Segregation and Monocyte DNA Methylation Age Acceleration

Hicken,

Dou,

Kershaw

et al. 2023

JAMA Netw Open

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ImportanceNeighborhood segregation and poverty may be important drivers of health inequities. Epigenomic factors, including DNA methylation clocks that may mark underlying biological aging, have been implicated in the link between social factors and health.ObjectiveTo examine the associations of neighborhood segregation and poverty with 4 DNA methylation clocks trained to capture either chronological age or physiological dysregulation.Design, Setting, and ParticipantsThis cohort study uses data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study that started in 2000 to 2002, with follow-up in 2002 to 2004, 2004 to 2005, 2005 to 2007, and 2010 to 2012. In 2000 to 2002, adults who identified as White or Black race or Hispanic or Chinese ethnicity in 6 US sites (Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; Northern Manhattan, New York; and St. Paul, Minnesota) were sampled for recruitment. A random subsample of 4 sites (Maryland, North Carolina, New York, and Minnesota) were selected for inclusion in the MESA epigenomics ancillary study at examination 5 (2010-2012). Participants who identified as White or Black race or Hispanic ethnicity, were aged 45 to 84 years, and did not have clinical cardiovascular disease were included in this analysis. Data were analyzed from May 2021 to October 2023.ExposureInformation on 2000 census tract poverty and Getis-Ord G statistic segregation of Hispanic residents, non-Hispanic Black residents, or non-Hispanic White residents were linked to participant addresses at examination 1 (2000-2002).Main Outcomes and MeasuresAt examination 5, DNA methylation was measured in purified monocytes. DNA methylation age acceleration was calculated using 4 clocks trained on either chronological age or physiological dysregulation. Linear regressions were used to test associations.ResultsA total of 1102 participants (mean [SD] age, 69.7 [9.4] years; 562 [51%] women) were included, with 348 Hispanic participants, 222 non-Hispanic Black participants, and 533 non-Hispanic White participants. For non-Hispanic Black participants, living in tracts with greater segregation of Black residents was associated with GrimAge DNA methylation age acceleration, a clock designed to capture physiological dysregulation. A 1-SD increase in segregation was associated with 0.42 (95% CI, 0.20-0.64) years age acceleration (P &lt; .001); this association was not observed with other clocks. This association was particularly pronounced for participants living in high poverty tracts (interaction term, 0.24; 95% CI, 0.07-0.42; P = .006). In the overall sample, census tract poverty level was associated with GrimAge DNA methylation age acceleration (β = 0.45; 95% CI, 0.20-0.71; adjusted P = .005).Conclusions and RelevanceThese findings suggest that epigenomic mechanisms may play a role in the associations of segregated and poor neighborhoods with chronic conditions.

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Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: The multi-ethnic study of atherosclerosis

Cited by 164 publications

References 61 publications

Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood

Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood

Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging

Racial and Ethnic Residential Segregation and Monocyte DNA Methylation Age Acceleration

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