Figure 2.

Overview of functional annotation pipeline. We expanded the search from 52 lead SNPs to include variants in LD (r²>0.5), leading to 4620 candidate variants. Of these, 74 overlapped one or more regulatory feature of interest: differentially acetylated (H3K27ac) regions between HCM and control patients, differentially expressed promoter regions between HCM and control patients, and super-enhancers specific to HCM or LV. In the 20 loci where these overlaps were observed, differential expression analysis on HCM patients and controls and or/eQTL mapping in LV identified 32 candidate genes. Eighteen of these validate the findings of the previous study ⁵, now also pinpointing causal variants and the potential mechanisms by which they account risk. In addition, 14 new candidate genes were identified, some with cardiac function and previously implicated in other studies on ECG traits (Table 2, Supplemental Tables 1 and 7).