Fig. 3: A highly polymorphic coding CCA repeat in HRCT1 is associated with risk of hypertension.

A Results of PheWAS for the TR in HRCT1. Traits are grouped into physiological categories (x-axis) plotted against the −log₁₀ Bonferroni-corrected p value per trait (y-axis). Significant fine-mapped associations are individually labeled and shown as filled red points to indicate negative directionality of effect. P values were calculated using linear and logistic regression implemented in REGENIE, applying a Bonferroni correction based on 9531 independent traits and 36,085 TRs analyzed. B Relative risk of high blood pressure versus average length of the HRCT1 CCA repeat. Odds ratio per allele is shown by the black dot with vertical lines representing the 95% confidence intervals. Odds ratios are based on analysis of 167,533 individuals with both genotype and phenotype data, with each odds ratio per and CI plotted per allele size calculated from at least 54 individuals. The bar plot above shows the relative frequency of averaged TR alleles in the UKB cohort. C Screenshot from the UCSC Genome Browser showing the location of the poly(CCA) motif within HRCT1. D Length of the HRCT1 CCA repeat (red dot) is the most strongly associated variant in the region with high blood pressure. P-values were calculated using logistic regression implemented in REGENIE. E Results after conditioning the same SNVs as shown in (D) based on average genotype of the HRCT1 repeat. The horizontal dashed line indicates the Bonferroni-significance threshold of p < 1.45 × 10⁻¹⁰. P values were calculated using logistic regression implemented in REGENIE. F Fine-mapping analysis of variants in the HRCT1 locus with CAVIAR ranks the poly(CCA) motif within HRCT1 (red dot) as the most likely variant underlying risk of high blood pressure.