Abstract | CONTEXT: 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.
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Authors | Nicola Santoro, Ling Chen, Jennifer Todd, Jasmin Divers, Amy S Shah, Samuel S Gidding, Brian Burke, Morey Haymond, Leslie Lange, Santica Marcovina, Jason Flannick, Sonia Caprio, Jose C Florez, Shylaja Srinivasan |
Journal | Journal of the Endocrine Society
(J Endocr Soc)
Vol. 5
Issue 11
Pg. bvab139
(Nov 01 2021)
ISSN: 2472-1972 [Electronic] United States |
PMID | 34568709
(Publication Type: Journal Article)
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Copyright | © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. |