Differential blood DNA methylation loci between Native Hawaiian and White women are associated with dietary patterns and metabolic biomarkers

Epigenetic differences across racial/ethnic groups can provide insights into health disparities, including likely mechanisms and multifactorial upstream exposures at play. We compared the blood DNA methylome of Native Hawaiian (NatH) women, an understudied group with high chronic disease burden, with that of White women. Blood genome-wide DNA methylation profiling was performed in generally healthy, non-smoking NatH (n = 143) and White (n = 181) postmenopausal women in the Multiethnic Cohort. CpGs showing significant (Bonferroni p < 0.05) and substantial (delta-beta > 0.1) differential methylation in NatH compared to White women (CpGs-NatH) were identified through linear regression of methylation, adjusted for potential confounders. The CpGs-NatH were examined for gene pathways and for associated dietary patterns and metabolic biomarkers. We identified 736 CpGs-NatH, which presented more frequent CpG island hypermethylation than expected. Many corresponding CpGs-NatH genes (61%) were functionally implicated in liver disease etiology, and 15 CpGs-NatH were correlated with MRI-quantified liver fat content. 168 of the 736 CpGs were associated with adherence to the Dietary Approaches to Stop Hypertension (DASH) diet. The CpGs-NatH were also associated with several blood biomarkers of key metabolism, including adiponectin, triglycerides, and sex hormone-binding globulin. Our findings suggest marked racial differences in DNA methylation, suggesting epigenetic mechanisms underlying racial metabolic health disparities, such as the higher propensity for ectopic fat accumulation and higher incidence of liver disease and cancer among NatH, compared to Whites. These results support further investigation of the epigenome across racial and ethnic populations in relation to lifestyle factors and metabolism.