Abstract
Context
Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood.
Objective
To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study (GWAS).
Design, participants and main outcome measures
We genotyped 206,928 variants and imputed 17,642,824 variants in 1,076 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, low-density lipoprotein (LDL-c) and high-density lipoprotein (HDL-c) concentrations adjusted for the genetic relationship matrix within each sub-study followed by meta-analyses for each trait.
Results
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 (P=2.3×10 -8) with each risk allele increasing triglycerides by 20%. We also identified a genome-wide significant signal at rs247617 (P=5.1×10 -9) between HERFUD1 and CETP associated with HDL-c, with carriers of one copy of the risk allele having twice higher HDL-c.
Conclusions
Our genetic analyses of lipid traits in youth with T2D have identified one novel and one previously known locus. Additional studies are needed to further characterize the genetic architecture of dyslipidemia in youth with T2D.
A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants
