Fig. 2: Genetic correlation of LV traits and HCM and use of MTAG to empower locus discovery.

Pairwise genetic correlation between LV traits shown in heatmap as absolute values (|rg_LV|) ranging from 0 (white) to 1 (red). LV traits are sorted into three clusters based on |rg_LV| along the x and y axes using Euclidean distance and complete hierarchical clustering: LV contractility (blue), volume (bluish green) and mass (orange) (see dendrogram on top). The table in the middle shows the individual LV trait h²_SNP and genetic correlation with HCM (rg_HCM), with corresponding s.e. The trait with the strongest correlation (based on rg_HCM) in each of the three clusters was carried forward for MTAG to empower locus discovery in HCM. MTAG resulted in an increase in N_eff, based on number of cases and controls and increase in mean χ² statistic from 21,725 to 28,106, with an estimated maxFDR of 0.027. Since strain^circ and strain^long are negative values where increasingly negative values reflect increased contractility, we show −strain^circ and −strain^long to facilitate interpretation of rg_HCM sign. Full rg_LV and rg_HCM results are shown in Supplementary Table 7.