Ancestry-attenuated effects of socioeconomic deprivation on type 2 diabetes disparities in the All of Us cohort

BACKGROUND: Diabetes is a common disease with a major burden on morbidity, mortality, and productivity. Type 2 diabetes (T2D) accounts for roughly 90% of all diabetes cases in the USA and has a greater observed prevalence among those who identify as Black or Hispanic. METHODS: This study aimed to assess T2D racial and ethnic disparities using the All of Us Research Program data and to measure associations between genetic ancestry (GA), socioeconomic deprivation, and T2D. We used the All of Us Researcher Workbench to analyze T2D prevalence and model its associations with GA, individual-level (iSDI), and zip code-based (zSDI) socioeconomic deprivation indices among participant self-identified race and ethnicity (SIRE) groups. RESULTS: The study cohort of 86,488 participants from the four largest SIRE groups in All of Us: Asian (n = 2311), Black (n = 16,282), Hispanic (n = 16,966), and White (n = 50,292). SIRE groups show characteristic genetic ancestry patterns, consistent with their diverse origins, together with a continuum of ancestry fractions within and between groups. The Black and Hispanic groups show the highest levels of socioeconomic deprivation, followed by the Asian and White groups. Black participants show the highest age- and sex-adjusted T2D prevalence (21.9%), followed by the Hispanic (19.9%), Asian (15.1%), and White (14.8%) groups. Minority SIRE groups and socioeconomic deprivation, both iSDI and zSDI, are positively associated with T2D, when the entire cohort is analyzed together. However, SIRE and GA both show negative interaction effects with iSDI and zSDI on T2D. Higher levels of iSDI and zSDI are negatively associated with T2D in the Black and Hispanic groups, and higher levels of iSDI and zSDI are negatively associated with T2D at high levels of African and Native American ancestry. CONCLUSIONS: Socioeconomic deprivation is associated with a higher prevalence of T2D in Black and Hispanic minority groups, compared to the majority White group. Nonetheless, socioeconomic deprivation is associated with reduced T2D risk within the Black and Hispanic groups. These results are paradoxical and have not been reported elsewhere, with possible explanations related to the nature of the All of Us data along with SIRE group differences in access to healthcare, diet, and lifestyle.