A genome-wide association study and genetic risk score for age at diabetes diagnosis support beta-cell dysfunction in young-onset diabetes in Chinese.

Three genome-wide significant loci—CDKAL1 (rs2206734), PAX4 (rs61160304), and KCNQ1 (rs2299620)—are linked to younger age at type 2 diabetes diagnosis in Chinese.

• Why it matters: Young-onset diabetes with age-at-diagnosis under 40 is clinically important, but the genetic variants and risk stratification tools specific to Chinese individuals remain incomplete.
• What they did: In 22,611 Chinese individuals with type 2 diabetes, GWAS and replication identified ADD signals, and an ADD genetic risk score (ADD-GRS) built from independent variants (p<5E-08) was tested against glycemic traits in diabetes and non-diabetes cohorts.
• The result: ADD-GRS predicts younger ADD and lower C-peptide with higher HbA1c, and it is linked to beta-cell–related T2D PRS; additionally, LINC02783/PADI1 and TARS2P1 show suggestive associations with YOD versus later-onset diabetes.

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