Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits
Nature Communications, 2025
Petty L., Chen H., Frankel E., Zhu W., Downie C., Graff M., Lin P., Sharma P., Zhang X., Scartozzi A., Roshani R., Landman J., Boehnke M., Bowden D., Chambers J., Mahajan A., McCarthy M., Ng M., Sim X., Spracklen C., Zhang W., Preuss M., Bottinger E., Nadkarni G., Loos R., Chen Y., Tan J., Ipp E., Genter P., Emery L., Louie T., Sofer T., Stilp A., Taylor K., Xiang A., Buchanan T., Roll K., Gao C., Palmer N., Norris J., Wagenknecht L., Nousome D., Varma R., McKean-Cowdin R., Guo X., Hai Y., Hsueh W., Sandow K., Parra E., Cruz M., Valladares-Salgado A., Wacher-Rodarte N., Rotter J., Goodarzi M., Rich S., Bertoni A., Raffel L., Nadler J., Kandeel F., Duggirala R., Blangero J., Lehman D., DeFronzo R., Thameem F., Wang Y., Gahagan S., Blanco E., Burrows R., Huerta-Chagoya A., Florez J., Tusie-Luna T., González-Villalpando C., Orozco L., Haiman C., Hanis C., Rohde R., Whitsel E., Reiner A., Kooperberg C., Li Y., Duan Q., Lee M., Correa-Burrows P., Fried S., North K., McCormick J., Fisher-Hoch S., Gamazon E., Morris A., Mercader J., Highland H., Below J.,
Disease area | Application area | Sample type | Products |
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Metabolic Diseases | Cross-platform Validation | Olink Explore 3072/384 |
Abstract
Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.