Genetics
A genome-wide significant signal near CETP is linked to doubled HDL cholesterol in youth with type 2 diabetes (J Endocr Soc 2021)
Original title: Genome-wide Association Study of Lipid Traits in Youth With Type 2 Diabetes
In 1076 youth (mean age 15.0 years) with type 2 diabetes from the TODAY and SEARCH for Diabetes in Youth studies, part of the ProDiGY consortium, researchers performed a genome-wide association study genotyping 206 928 variants and imputing 17 642 824 variants to identify genetic determinants of lipid traits. A novel deletion on chromosome 3 reached genome-wide significance for triglycerides (P = 2.3 × 10-8), with each risk allele raising triglycerides by 20%. A genome-wide significant signal at rs247617, between HERFUD1 and CETP, was associated with HDL cholesterol (P = 5.1 × 10-9), with carriers of one copy of the risk allele having roughly twice as high HDL cholesterol, identifying a strong CETP-region genetic effect on HDL cholesterol specifically in youth with type 2 diabetes.
Original 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.
Design Participants And Main Outcome Measures: 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.
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 1 copy of the risk allele having twice higher HDL-c.
Conclusions: 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.