Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study

Abstract

Background Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA). Methods Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60–65. Differentially methylated CpGs by race/ethnicity (DM-CpGs) were identified by linear regression (Bonferroni-corrected P < 0.1) and analyzed in relation to corresponding gene expression, a priori selected single nucleotide polymorphisms (SNPs), and blood biomarkers of inflammation and metabolism using Pearson or Spearman correlations (FDR < 0.1). Results We identified 174 DM-CpGs with the majority of hypermethylated in JPA compared to EUA (n = 133), often in promoter regions (n = 48). Half (51%) of the genes corresponding to the DM-CpGs were involved in liver function and liver disease, and the methylation in nine genes was significantly correlated with gene expression for DM-CpGs. A total of 156 DM-CpGs were associated with rs7489665 (SH2B1). Methylation of DM-CpGs was correlated with blood levels of the cytokine MIP1B (n = 146). We confirmed some of the DM-CpGs in the TCGA adjacent non-tumor liver tissue of Asians versus EUA. Conclusion We found a number of differentially methylated CpGs in blood DNA between JPA and EUA women with a potential link to liver disease, specific SNPs, and systemic inflammation. These findings may support further research on the role of DNA methylation in mediating some of the higher risk of liver disease among JPA.

Sex-specific DNA methylation in saliva from the multi-ethnic Future of Families and Child Wellbeing Study

“…Principal component analysis of the methylation data revealed that cell-type composition, sex, and sample plate were associated with individual PCs ( Supplemental Figure S4 ) and were thus controlled for in subsequent sex-specific analyses. We also adjusted for mother’s self-reported race/ethnicity to account for race/ethnic and/or ancestry differences in DNAm patterns, which have been reported in the literature [ 42 , 43 ].…”

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women

“…Race/ethnicity was included in the analysis due to known associations with DNA methylation. 78 , 79 , 80 …”

Identification of differentially methylated regions in rare diseases from a single-patient perspective

“…Statistical testing was always performed on M values and not beta values due to their statistical properties. A “black list” of CpGs known to be involved in BMI [ 11 , 12 ], aging [ 9 ], smoking status [ 13 ], and ethnicity [ 10 ] was compiled (Additional file 1 : File S1, Table 3). DMRs containing any of those CpGs were removed.…”

“…DNA methylation (DNAm) of cytosines (5-mC) plays an important role in cell biology, most notably in tissue-specific regulation of gene expression. Other roles include X-chromosome inactivation, regulation of splice junctions, and genomic imprinting [ 1 , 2 ] Differential methylation of cytosines, or epivariation, has been linked to a wide array of diseases such as cancer, aging, metabolic, cardiovascular, neurodevelopmental, and autoimmune disorders [ 3 – 9 ], as well as other variables like the body mass index (BMI), smoking status or ethnicity [ 10 – 13 ]. Differential methylation can occur either at single cytosines (DMCs) or affect several loci within a region, resulting in differentially methylated regions (DMRs).…”