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- Title
The First Genome-Wide Association Study for Type 2 Diabetes in Youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortium.
- Authors
Srinivasan, Shylaja; Chen, Ling; Todd, Jennifer; Divers, Jasmin; Gidding, Samuel; Chernausek, Steven; Gubitosi-Klug, Rose A.; Kelsey, Megan M.; Shah, Rachana; Black, Mary Helen; Wagenknecht, Lynne E.; Manning, Alisa; Flannick, Jason; Imperatore, Giuseppina; Mercader, Josep M.; Dabelea, Dana; Florez, Jose C.; ProDiGY Consortium.
- Abstract
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 PHF2 (P = 3.2 × 10-8; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P = 8.0 × 10-20; OR 1.58), rs72982988 near MC4R (P = 4.4 × 10-14; OR 1.53), rs200893788 in CDC123 (P = 1.1 × 10-12; OR 1.32), rs2237892 in KCNQ1 (P = 4.8 × 10-11; OR 1.59), rs937589119 in IGF2BP2 (P = 3.1 × 10-9; OR 1.34), and rs113748381 in SLC16A11 (P = 4.1 × 10-8; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in CPEB2 (P = 3.2 × 10-8; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes.
- Subjects
TYPE 2 diabetes; GENETICS; DIABETES; GENETIC models; ODDS ratio; METABOLIC regulation; PROTEINS; RESEARCH; SEQUENCE analysis; RESEARCH methodology; CELL receptors; GENETIC polymorphisms; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; DISEASE susceptibility; RESEARCH funding; MEMBRANE proteins
- Publication
Diabetes, 2021, Vol 70, Issue 4, p996
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db20-0443