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 United States and has greater observed prevalence among those who identify as Black or Hispanic. METHODS: The aims of this study were to determine whether T2D racial and ethnic disparities can be observed in data from the All of Us Research Program and to measure associations of genetic ancestry (GA) and socioeconomic deprivation with T2D. The All of Us Researcher Workbench was used to calculate T2D prevalence and to model T2D associations with GA, individual-level (iSDI) and zip code-based (zSDI) socioeconomic deprivation indices within and between 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=2,311), 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 median SDI values, 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 are positively associated with T2D, when the entire cohort is analyzed together. However, SIRE and GA both show negative interaction effects with SDI on T2D. Higher levels of SDI are negatively associated with T2D in the Black and Hispanic groups, and higher levels of SDI are negatively associated with T2D at high levels of African and Native American ancestry. CONCLUSION: Socioeconomic deprivation is positively associated with the SIRE group T2D disparities observed here but negatively associated with T2D within the Black and Hispanic groups that show the highest T2D prevalence. These results are paradoxical and have not been reported elsewhere. We discuss possible explanations for this paradox related to the nature of the All of Us data along with SIRE group differences in access to healthcare, diet, and lifestyle.