The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabete Show more
The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in Show less
Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood. To evaluate the genetic determinants of lip Show more
Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood. To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study. We genotyped 206 928 variants and imputed 17 642 824 variants in 1076 youth (mean age 15.0 ± 2.48 years) with T2D from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) studies as part of the Progress in Diabetes Genetics in Youth (ProDiGY) consortium. We performed association testing for triglyceride and low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-c) concentrations adjusted for the genetic relationship matrix within each substudy followed by meta-analyses for each trait. We identified a novel association between a deletion on chromosome 3 (3:67817380_AT/A_Deletion:RP11-81N13.1) and triglyceride levels at genome-wide level of significance ( Our genetic analyses of lipid traits in youth with T2D have identified 1 novel and 1 previously known locus. Additional studies are needed to further characterize the genetic architecture of dyslipidemia in youth with T2D. Show less