Fig. 2: Increased polygenic risk associated with earlier and more severe diabetes diagnosis in HNF-MODY.
From: Common genetic variants modify disease risk and clinical presentation in monogenic diabetes
a, Association between polygenic scores for upper-level diabetes-related traits and age of diabetes diagnosis. Estimates were derived using a mixed-effects linear model with family as a random effect and adjusted for other polygenic scores and the first ten within-cohort principal components. b, Association between polygenic scores and risk of severe diabetes (defined as HbA1c ≥ 8.5% or insulin treatment at recruitment), using a mixed-effects logistic model with the same covariates as in a. In total, 676 out of 1,462 MODY carriers met the criteria for severe diabetes. c,d, Association of T2D-partitioned risk scores with age of diabetes diagnosis (c) and diabetes severity (d), estimated using linear mixed-effects models adjusted for the first ten within-cohort principal components. Dots represent the estimates, with lines indicating 95% CIs. Asterisks highlight significant differences (P < 0.0056), after Bonferroni correction. Estimates represent the effect of a 1 s.d. increase in the respective polygenic score. All analyses in a–d were conducted in 1,462 MODY cases.
