Accounting for Life-Course Exposures in Epigenetic Biomarker Association Studies: Early Life Socioeconomic Position, Candidate Gene DNA Methylation, and Adult Cardiometabolic Risk

Overview

Journal Am J Epidemiol

Publisher Oxford University Press

Specialty Public Health

Date 2016 Sep 22

PMID 27651384

Citations 16

Authors

Jonathan Y Huang

Amelia R Gavin

Thomas S Richardson

Ali Rowhani-Rahbar

David S Siscovick

Hagit Hochner

Yechiel Friedlander

Daniel A Enquobahrie

Affiliations

Soon will be listed here.

Abstract

Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007-2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes (ABCA1, INS-IGF2, LEP, HSD11B2, and NR3C1). We used multivariable linear regression and marginal structural models to estimate associations under 2 causal structures for life-course exposures and timing of methylation measurement. We also examined whether methylation was associated with adult cardiometabolic phenotype. Higher maternal education was consistently associated with higher HSD11B2 methylation (e.g., 0.5%-point higher in 9-12 years vs. ≤8 years, 95% confidence interval: 0.1, 0.8). Higher HSD11B2 methylation was also associated with lower adult weight and total and low-density lipoprotein cholesterol. We found that associations with early life socioeconomic position measures were insensitive to different causal assumption; however, exploratory analysis did not find evidence for a mediating role of methylation in socioeconomic position-cardiometabolic risk associations.

Citing Articles

Epigenome-wide association study of incident type 2 diabetes in Black and White participants from the Atherosclerosis Risk in Communities Study.

Venkataraghavan S, Pankow J, Boerwinkle E, Fornage M, Selvin E, Ray D Diabetologia. 2025; .

PMID: 39971753 DOI: 10.1007/s00125-024-06352-9.

DNA methylation signatures as biomarkers of socioeconomic position.

Rajaprakash M, Dean L, Palmore M, Johnson S, Kaufman J, Fallin D Environ Epigenet. 2023; 9(1):dvac027.

PMID: 36694711 PMC: 9869656. DOI: 10.1093/eep/dvac027.

Genetically predicted higher educational attainment decreases the risk of stroke: a multivariable Mendelian randomization study.

Zhang W, Li Y, Li Y, Zheng K, Zou S, Jia X BMC Cardiovasc Disord. 2022; 22(1):269.

PMID: 35710362 PMC: 9205080. DOI: 10.1186/s12872-022-02713-7.

Understanding Health Inequalities Through the Lens of Social Epigenetics.

Martin C, Ghastine L, Lodge E, Dhingra R, Ward-Caviness C Annu Rev Public Health. 2022; 43:235-254.

PMID: 35380065 PMC: 9584166. DOI: 10.1146/annurev-publhealth-052020-105613.

Associations between indicators of socioeconomic position and DNA methylation: a scoping review.

Cerutti J, Lussier A, Zhu Y, Liu J, Dunn E Clin Epigenetics. 2021; 13(1):221.

PMID: 34906220 PMC: 8672601. DOI: 10.1186/s13148-021-01189-0.

References

Coolen M, Statham A, Gardiner-Garden M, Clark S . Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Res. 2007; 35(18):e119. PMC: 2094090. DOI: 10.1093/nar/gkm662. View

Sharp G, Lawlor D, Richmond R, Fraser A, Simpkin A, Suderman M . Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children. Int J Epidemiol. 2015; 44(4):1288-304. PMC: 4588865. DOI: 10.1093/ije/dyv042. View

Li L, Dahiya R . MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002; 18(11):1427-31. DOI: 10.1093/bioinformatics/18.11.1427. View

Turan N, Ghalwash M, Katari S, Coutifaris C, Obradovic Z, Sapienza C . DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?. BMC Med Genomics. 2012; 5:10. PMC: 3359247. DOI: 10.1186/1755-8794-5-10. View

Radtke K, Ruf M, Gunter H, Dohrmann K, Schauer M, Meyer A . Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl Psychiatry. 2012; 1:e21. PMC: 3309516. DOI: 10.1038/tp.2011.21. View

Gavin A, Hill K, Hawkins J, Maas C . The role of maternal early-life and later-life risk factors on offspring low birth weight: findings from a three-generational study. J Adolesc Health. 2011; 49(2):166-71. PMC: 3867286. DOI: 10.1016/j.jadohealth.2010.11.246. View

Essex M, Boyce W, Hertzman C, Lam L, Armstrong J, Neumann S . Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Dev. 2011; 84(1):58-75. PMC: 3235257. DOI: 10.1111/j.1467-8624.2011.01641.x. View

Talens R, Christensen K, Putter H, Willemsen G, Christiansen L, Kremer D . Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell. 2012; 11(4):694-703. PMC: 3399918. DOI: 10.1111/j.1474-9726.2012.00835.x. View

Cohen E, Krause I, Fraser A, Goldberg E, Garty M . Hyperuricemia and metabolic syndrome: lessons from a large cohort from Israel. Isr Med Assoc J. 2012; 14(11):676-80. View

10.

Appleton A, Armstrong D, Lesseur C, Lee J, Padbury J, Lester B . Patterning in placental 11-B hydroxysteroid dehydrogenase methylation according to prenatal socioeconomic adversity. PLoS One. 2013; 8(9):e74691. PMC: 3764127. DOI: 10.1371/journal.pone.0074691. View

11.

Sauerbrun-Cutler M, Segars J . Do in utero events contribute to current health disparities in reproductive medicine?. Semin Reprod Med. 2013; 31(5):325-32. PMC: 4152851. DOI: 10.1055/s-0033-1348890. View

12.

Tobi E, Lumey L, Talens R, Kremer D, Putter H, Stein A . DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009; 18(21):4046-53. PMC: 2758137. DOI: 10.1093/hmg/ddp353. View

13.

Lanza H, Grella C, Chung P . Does adolescent weight status predict problematic substance use patterns?. Am J Health Behav. 2014; 38(5):708-16. PMC: 4066210. DOI: 10.5993/AJHB.38.5.8. View

14.

Hochner H, Friedlander Y, Calderon-Margalit R, Meiner V, Sagy Y, Avgil-Tsadok M . Associations of maternal prepregnancy body mass index and gestational weight gain with adult offspring cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-up Study. Circulation. 2012; 125(11):1381-9. PMC: 3332052. DOI: 10.1161/CIRCULATIONAHA.111.070060. View

15.

Ehrich M, Nelson M, Stanssens P, Zabeau M, Liloglou T, Xinarianos G . Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci U S A. 2005; 102(44):15785-90. PMC: 1276092. DOI: 10.1073/pnas.0507816102. View

16.

Talens R, Jukema J, Trompet S, Kremer D, Westendorp R, Lumey L . Hypermethylation at loci sensitive to the prenatal environment is associated with increased incidence of myocardial infarction. Int J Epidemiol. 2011; 41(1):106-15. PMC: 3663184. DOI: 10.1093/ije/dyr153. View

17.

Dominguez-Salas P, Moore S, Baker M, Bergen A, Cox S, Dyer R . Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014; 5:3746. PMC: 4015319. DOI: 10.1038/ncomms4746. View

18.

Imai K, Keele L, Tingley D . A general approach to causal mediation analysis. Psychol Methods. 2010; 15(4):309-34. DOI: 10.1037/a0020761. View

19.

Richmond R, Al-Amin A, Davey Smith G, Relton C . Approaches for drawing causal inferences from epidemiological birth cohorts: a review. Early Hum Dev. 2014; 90(11):769-80. PMC: 5154380. DOI: 10.1016/j.earlhumdev.2014.08.023. View

20.

Drake A, Seckl J . Transmission of programming effects across generations. Pediatr Endocrinol Rev. 2012; 9(2):566-78. View