Fig. 3: Associations of HF risk variants with traits relating to disease subtypes and risk factors.

This bubble plot shows associations between the identified HF loci and risk factors and quantitative imaging traits, using summary estimates from UK Biobank (DCM, dilated cardiomyopathy) and published GWAS summary statistics. Number in bracket represents sample size (for quantitative traits) or number of cases (for binary traits) used to derive the GWAS summary statistics. The size of the bubble represents the absolute Z-score for each trait, with the direction oriented towards the HF risk allele. Red/blue indicates a positive/negative cross-trait association (i.e., increase/decrease in disease risk or increase/decrease in continuous trait). We accounted for family-wise error rate at 0.05 by Bonferroni correction for the ten traits tested per HF locus (P < 4.5e-4); traits meeting this threshold of significance for association are indicated by dark colour shading. Agglomerative hierarchical clustering of variants was performed using the complete linkage method, based on Euclidian distance. Where a sentinel variant was not available for all traits, a common proxy was selected (bold text). For the LPA locus, associations for the more common of the two variants at this locus are shown. Bold text represents variants whose estimates are plotted, upon which we performed hierarchical agglomerative clustering using the complete linkage method based on Euclidian distance. FS, fractional shortening; LVD, left ventricular dimension; DCM, dilated cardiomyopathy; AF, atrial fibrillation; CAD, coronary artery disease; LDL-C, low-density lipoprotein cholesterol; T2D, type 2 diabetes; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure.