Hispanic/Latino populations are both disproportionately burdened by type 2 diabetes (T2D) and drastically less studied compared to non-Hispanic whites. We present results of the final data freeze of the DIAMANTE Hispanic/Latino Consortium, comprising the largest genome-wide meta-analysis and transcriptome-wide association study of T2D in a Hispanic/Latino population and including a total of 13,151 T2D cases and 21,511 controls. We identified a novel locus in an intronic region of BACE1 for T2D adjusted for body mass index, which has previously been linked to gestational diabetes susceptibility, but never before to T2D. We also identified two variants in known loci with evidence (p <1x10-5) of a residual effect after adjusting for the closest known variant, suggesting that these may be population-specific effects due to H/L linkage disequilibrium structure. We used S-PrediXcan to compute the association of tissue-specific imputed expression for 48 tissues with T2D, revealing novel associations with ten genes and replicating six known genes. These novel genes include three genes previously associated with blood pressure traits: MOV10, ST7L, and WNT2B, as well as two genes previously associated with adiposity, measured by waist and hip circumference: MOV10 and WNT2B. Three novel genes have compelling evidence due to known roles of their biological pathways, including PTCH1, in the hedgehog pathway, which is known to play a role in pancreas development, ST7L, which is a miR-24 target and previous studies have indicated that miR-24 is elevated in diabetes, and WNT2B, part of the WNT signaling pathway, which is known to be involved in glucose homeostasis. These results demonstrate that genetic study of T2D in H/L populations can both help prevent a major health disparity through inclusion of this henceforth overlooked population and can also enable further discovery.
L.E. Petty: None. J.E. Below: None.
