Fig. 5: Effect of the VIPs versus confirmed pathogenic MODY variants on diabetes risk and related clinical variables.

a–c, Forest plots showing the effect of p.Arg114Trp, p.Pro475Leu and p.Val455Glu, stratified by PRS tertiles. The ORs are denoted by boxes and the 95% CIs by horizontal lines. The P values are from the meta-analysis of two-sided logistic regression models, weighting the cohorts by the inverse of the s.e. for each variant. The ORs are relative to the noncarriers in the middle tertile of the PRS. On the top of each Forest plot, the effects of being a carrier for a confirmed pathogenic variant for HNF4A (a), HNF1A (b) and GCK (c) MODY genes are also represented, using data identified via exome sequencing in UKB³⁴. For each effect estimate, the diabetes case definition included individuals with T1D or T2D. d–f, Boxplots of HbA1c (%), random glucose (mg dl⁻¹) and BMI (kg m⁻²) in cases with diabetes and noncases among noncarriers (NCs, left), carriers of variants with intermediate penetrance (middle) and carriers of confirmed pathogenic MODY variants (right) in HNF4A (d), HNF1A (e) and GCK (f). The covariate-adjusted P value is included for comparisons with significant differences (^*P < 0.05, ^**P < 0.001, ^***P < 0.0001) between groups using two-sided Wilcoxon’s rank-sum tests. Boxplots indicate the group median (central line), first and third quartiles (bounds of box) and 1.5× interquartile range (whiskers).