Publication Description
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
(
= 3.2 × 10
; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in
(
= 8.0 × 10
; OR 1.58), rs72982988 near
(
= 4.4 × 10
; OR 1.53), rs200893788 in
(
= 1.1 × 10
; OR 1.32), rs2237892 in
(
= 4.8 × 10
; OR 1.59), rs937589119 in
(
= 3.1 × 10
; OR 1.34), and rs113748381 in
(
= 4.1 × 10
; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in
(
= 3.2 × 10
; 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.