Fig. 2

Age of disease onset for PAH Biobank cases with rare deleterious variants in known PAH risk genes. a Box plots showing median, interquartile range, and min/max values for age of disease onset (i.e., age at diagnostic right heart catheterization). The number of cases carrying variants for each gene is given above each box plot. Genes represented by less than four cases are not shown. b Histogram plots showing age-of-onset distributions for the whole cohort (n = 2572), BMPR2 (n = 180), or TBX4 (n = 23) variant carriers. Red vertical lines indicate the group means. BMPR2 carriers had a younger mean age of onset (mean = 37 years, SD = 15; Mann-Whitney U test, p = 1.1E−15) but no enrichment of child-onset cases (binomial test p = 1, RR = 0.93) compared to the whole cohort, whereas TBX4 carriers had a younger mean age of onset (mean = 29 years, SD = 25; Mann-Whitney U test, p = 0.001) and significant enrichment of child-onset cases (binomial test p = 6.5E−08, RR = 12.3) compared to the whole cohort