Fig. 1. Scheme of the study and genetic discovery.

a, Whole-exome sequence data of individuals with youth-onset T2D were matched to those of external non-diabetic control participants using genetic principal components and a singular-value decomposition (SVD)-based method resulting in 3,005 cases and 9,777 control participants for single-variant and gene-level association analysis. b, Single-variant association analysis revealed four variants passing exome-wide significance (P < 4.3 × 10⁻⁷). c, Gene-level association analysis showed three genes associated with youth-onset T2D at exome-wide significance (P < 2.6 × 10⁻⁶). Blue dots represent previously known variants or genes of adult-onset T2D. Both single-variant and gene-level association analyses were performed with Firth’s penalized logistic regression. GATK, genome analysis toolkit; PC, principal components; WES, whole-exome sequencing.