A type 2 diabetes DNA methylation signature in monocytes exhibits ethnic specificity preferentially for Native Hawaiians. A type 2 diabetes DNA methylation signature in monocytes exhibits ethnic specificity preferentially for Native Hawaiians

Type 2 diabetes (T2D) is among the leading causes of death in the U.S. Ethnic differences in T2D prevalence are evident, including especially for Native Hawaiians (NHs) who remain disproportionately affected by it. This difference in T2D susceptibility involves an interplay between genetic and environmental factors, of which epigenetic mechanisms, including DNA methylation (DNAm) provide a novel approach to investigating gene-environment interactions of health and disease. Monocytes, an innate immune cell intrinsic to the inflammatory response, are a fundamental immune cell component that likely underlies T2D pathogenesis, given their involvement in inflammation and inflammation-associated insulin resistance and metabolic dysfunction. From participants enrolled into the Multiethnic Cohort Study (MEC), who self-identified as NH (n=152), Japanese American (JA; n=119), or White (n=121), we investigated monocyte-specific DNAm patterns in participants at a baseline visit, when free of T2D, using the HumanMethylation850K (850K) to determine whether monocytes harbor an ethnic-specific epigenetic signature of T2D risk that precedes T2D diagnosis. Using an epigenome-wide association study (EWAS), we found 904 significantly (q 65% monocytes) from 391 participants enrolled into the Multiethnic Cohort Study were analyzed using the Infinium HumanMethylation850 (850K), including 152 Native Hawaiians, 119 Japanese Americans, and 121 Whites, of which 171 participants would be diagnosed with T2D by the follow-up visit 15 years later (incident T2D) and 214 would remain T2D-free (controls).