Fig. 2: Morphological characterization of the GDF5 GROW1 enhancer and rs4911178 variant in patients and the mouse model.

a Higher acetabular inclination angle and acetabular index along with lower center-edge angle in homozygous “A/A” risk DDH patients compared to heterozygous “A/G” controls (HET n = 25, HOMO n = 83). Independent t-tests with two-sided p-values were used. Bars indicate medians. b GROW1-driven lacZ expression in growth zone chondrocytes of the acetabulum and proximal femoral neck and trochanteric regions at E15.5. Acetabulum (Ac), Head (He), Neck (Ne), Trochlea (Tr) and Condyles (Co) (red text denotes locations of expression, black text indicates no expression). c µCT measurements of significantly affected anatomical features in GROW1 null mice at postnatal day, P30 (WT n = 7, HET n = 12, HOMO n = 12). ANOVA with Dunnet post-hoc was used for pairwise comparisons to wild type. All p-values are two-sided and indicate significant differences compared to wild type. Bars indicate medians. d µCT measurements of significantly affected anatomical features in rs4911178 single base-pair replacement mice at postnatal day, P56 (WT n = 12, HET n = 42, HOMO n = 14). ANOVA with Dunnet post-hoc was used for pairwise comparisons to wild type. All p-values are two-sided and indicate significant differences compared to wild type. Bars indicate medians. e 3D comparative analysis indicating the anatomical locations of largest morphological differences between wild type GROW1^+/+ and homozygous GROW1^−/− hind limbs (top) as well as between wild type GROW1^{rs4911178-G/rs4911178-G} and homozygous risk GROW1^{rs4911178-A/rs4911178-A} hind limbs (bottom). The areas with the largest variations are highlighted in red (wild type > homozygous) and dark blue (wild type <  homozygous), with minimal variations displayed in green/yellow. Bars indicate medians. All p-values are two sided. See Supplementary Figs. 3 and 4, Supplementary Tables 2–8 and the Supplementary Information for related analyses.