Genome-Wide Analysis of Left Ventricular Maximum Wall Thickness in the UK Biobank Cohort Reveals a Shared Genetic Background With Hypertrophic Cardiomyopathy

Figures

• 

  Figure 1.. Automatic segmentation and derivation of left ventricular maximum wall thickness (LVMWT) in AHA-16 segment model. Images in the left-hand side show short-axis steady-state free precession cine cardiovascular magnetic resonance images of left and right ventricles with automatic segmentation masks (green=left ventricular myocardium, red=left ventricular blood pool and yellow=right ventricular blood pool) in the basal, mid and apical slices. Images in the right-hand side illustrate the corresponding left ventricular (LV) wall thickness measurements in the AHA-16 segment model.

• 

  Figure 2.. Manhattan plot of left ventricular maximum wall thickness genomic loci. Each point represents a genetic variant. The red line indicates the genome-wide significant threshold at P<5×10−8 and the blue line indicates the suggestive significance at P<1×10−5. P values are 2-sided based on the Chi-square test statistics in the BOLT-LMM software.

• 

  Figure 3.. Relationship between left ventricular maximum wall thickness (LVMWT) genetic risk score (GRS) and hypertrophic cardiomyopathy (HCM) status. The GRS was evaluated in all-comers, sarcomere-positive and sarcomere-negative HCM cases. A, A quintile-based analysis demonstrates how a GRS of susceptibility loci underpinning LVMWT show protective effects in the lowest 20% of the population compared with the middle 60%. Similarly, the upper 20% show increased susceptibility towards a risk of developing HCM compared with the middle 60%. These associations appear driven in the all comer HCM analysis by sarcomere negative HCM. B, A per-SD estimate is reported to facilitate comparison with other GRSs. Odds ratios (x axis) are reported, with error bars denoting 95% CI.

• 

  Figure 4.. Relationship between hypertrophic cardiomyopathy (HCM) genetic risk score (GRS) and phenotypic left ventricular maximum wall thickness (LVMWT). A, The association between the HCM GRS from Tadros et al and LVMWT. B, The association between the HCMR GRS from Harper et al and LVMWT. The gray line with the shaded area indicates the linear regression estimate with its 95% CI. The dots and the vertical error bars represent the mean and 95% CI of LVMWT in each HCM GRS decile group. GRS indicates genetic risk score; HCM, hypertrophic cardiomyopathy; and LVMWT, left ventricular maximum wall thickness.