Epigenome-wide association studies of three social determinants of health and implications for lung functions among survivors of childhood cancer
Carmen L. Wilson,
Kirsten K. Ness,
Kevin R. Krull,
Deo Kumar Srivastava,
Melissa M. Hudson,
Leslie L. Robison,
Posted 04 Nov 2020
medRxiv DOI: 10.1101/2020.10.30.20223313
Posted 04 Nov 2020
BackgroundEmerging evidence suggests that social determinants of health (SDOH) may influence health and wellness through an epigenetic mechanism in the general population. However, the social epigenomic approach has not yet been applied to survivors of childhood cancer, a vulnerable population with elevated risk for chronic health conditions (CHCs). MethodsStudy participants were drawn from the St Jude Lifetime Cohort, a hospital-based retrospective cohort with prospective follow up. DNA methylation (DNAm) profiling was generated based on blood derived DNA collected during follow-up visit. SDOH included educational attainment, personal income, and area deprivation index (ADI) based on baseline or follow-up questionnaires and geocoding. CHCs were clinically assessed with severity grade. ResultsWe included 258 childhood cancer survivors of African ancestry (AA) (median time from diagnosis=25.2 years, interquartile range [IQR]=19.9-32.1 years) and 1,618 survivors of European ancestry (EA) (median time from diagnosis=27.3, IQR=21.1-33.7 years). Through epigenome-wide association studies, we identified 130 SDOH-CpG associations including educational attainment (N=88), personal income (N=23), and ADI (N=19) at epigenome-wide significance level (P<9x10-8). There were 13 CpGs, commonly associated with all three SDOH factors, with attenuated remaining effect sizes (36.8-48.3%) after additionally adjusting body mass index and smoking, mapped to smoking-related genes including GPR55, CLDND1, CPOX, GPR15, AHRR, PRRC2B, and ELMSAN1. Among 130 SDOH-related CpGs, three independent CpGs (cg04180924, cg1120500, and cg27470486) had a significant combined mediation effect for educational attainment (%mediation=48.9%), and a single mediator cg08064403 was found with significant mediation effect for personal income (25.9%) and ADI (24.1%) on pulmonary diffusion deficit, which showed higher incidence in AA than in EA survivors implying racial disparity which is possibly due to more disadvantageous SDOH factors in AA than in EA. ConclusionsWe demonstrated striking DNAm signatures associated with multiple SDOH factors (educational attainment, personal income, and ADI) and many epigenome-wide significant CpG sites resembling the effect of smoking exposure. We also identified an exemplified racial health disparity in pulmonary diffusion deficit between AA and EA survivors and illuminated DNAm as potential mechanistic mediators for SDOH factors using a social epigenomic approach.
- Downloaded 125 times
- Download rankings, all-time:
- Site-wide: 149,489
- In epidemiology: 6,169
- Year to date:
- Site-wide: 102,777
- Since beginning of last month:
- Site-wide: 103,434
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!