Socioeconomic deprivation and genetic ancestry interact to modify type 2 diabetes ethnic disparities in the United Kingdom

BACKGROUND: Type 2 diabetes (T2D) is a complex common disease that disproportionately impacts minority ethnic groups in the United Kingdom (UK). Socioeconomic deprivation (SED) is widely considered as a potential explanation for T2D ethnic disparities in the UK, whereas the effect of genetic ancestry (GA) on such disparities has yet to be studied. METHODS: We leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010, to model the relationship between SED (Townsend index), GA (clustering principal components of whole genome genotype data), and T2D status (ICD-10 codes) across the three largest ethnic groups in the UK – Asian, Black, and White – using multivariable logistic regression. FINDINGS: The Asian group shows the highest T2D prevalence (17·9%), followed by the Black (11·7%) and White (5·5%) ethnic groups. We find that both SED (OR: 1·11, 95% CI: 1·10–1·11) and non-European GA (OR South Asian versus European: 4·37, 95% CI: 4·10–4·66; OR African versus European: 2·52, 95% CI: 2·23–2·85) are significantly associated with the observed T2D disparities. GA and SED show significant interaction effects on T2D, with SED being a relatively greater risk factor for T2D for individuals with South Asian and African ancestry, compared to those with European ancestry. INTERPRETATION: The significant interactions between SED and GA underscore how the effects of environmental risk factors can differ among ancestry groups, suggesting the need for group-specific interventions. FUNDING: This work was supported by the National Institutes of Health (NIH) Distinguished Scholars Program (DSP) to LMR and the Division of Intramural Research (DIR) of the National Institute on Minority Health and Health Disparities (NIMHD) at NIH.