Introduction and Objective: Type 2 diabetes (T2D), affecting 537 million individuals globally, disproportionately impacts Latin American populations, who experience higher rates of diabetic complications. Despite large-scale genomic studies identifying T2D-associated variants enriched in this population, many lie in non-coding regions, complicating the identification of causal genes. Existing genomics resources like GTEx were developed using data from primarily European populations, and do not cover Latin American associated variants. To address this, the LAGTEx project is generating the largest expression QTL resource from four insulin-sensitive tissues—subcutaneous and visceral adipose (SAT, N=301, VAT, N=309), liver (N=213), and skeletal muscle (N=90)—totaling 913 tissue samples from 360 participants of Latin American ancestry.Methods: Bulk RNA sequencing data was generated from SAT, VAT, liver, and muscle, and genotypes were collected from 360 participants of Latin American ancestry. Genotypes were imputed using the TOPMED reference panel and RNA-seq counts were normalized using the DESeq2 median ratio method to account for differences in sequencing depth and library composition. FastQTL was used to identify eQTLs that link genetic variants to gene expression variation, adjusting for covariates like age, sex, BMI, and batch.Results: We present results from our pilot analysis of 51 liver samples. We identified 23,424 eQTLs associated with variation in the expression of 440 genes. Effect sizes were consistent with those reported in GTEx liver eQTLs (rho: 0.754, p<2.2×10-300). Our results replicate the isoform-specific effects of a previously identified Latin American specific T2D protective splice acceptor variant in IGF2, with carriers showing reduced expression of IGF2 isoform 2.Conclusion: LAGTEx covers an important gap to assess gene expression effects of Latin American enriched variants in insulin target tissues, enhancing understanding of ancestry-specific genetic regulation of metabolic traits.
H. Wadhwa: None. L. Szczerbinski: None. F.M. Barajas-Olmos: None. K. Taylor: None. H. Garcia-Ortiz: None. C. Contreras-Cubas: None. A. Martínez-H: None. V. Kaur: None. A. Huerta: None. A. Janucik: None. A.J. Kretowski: None. M. Claussnitzer: None. I. Cebola: Research Support; Novo Nordisk, Gilead Sciences, Inc. Other Relationship; Ochre Bio. Research Support; British Heart Foundation, Wellcome Trust, Royal Society, NIHR Imperial Biomedical Research Centre, National Centre for the Replacement, Refinement & Reduction of Animals in Research. L. Orozco: None. J. Mercader: None.
American Diabetes Association (11-22-ICTSPM-16); FNIH (RFP6); NHGRI (U01HG011723); National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health (R01DK137993, U01 DK140757); Medical University of Bialystok (MUB) grant from the Ministry of Science and Higher Education (Poland)
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