Fig. 3: Lo-siRF finds epistasis between genetic risk loci for LV hypertrophy.
From: Epistasis regulates genetic control of cardiac hypertrophy
a, Circos plot illustrating genetic risk loci identified by lo-siRF (green, circle 2) and regions after clumping FUMA-extracted SNVs in LD (r2 > 0.6) with lo-siRF-prioritized SNVs (black, circle 3). Circle 1 shows the top 300 epistatic SNV–SNV pairs ranked by occurrence frequency in lo-siRF (green), SNV–gene linkages (FDR < 0.5) from GTEx37 v8 cis-eQTL data of heart and skeletal muscle tissues (purple), and 3D chromatin interactions33 from Hi-C data of LV tissue (GSE87112). Circle 5 and 6 show occurrence frequencies and the number of partner SNVs in epistasis (normalized by the maximum value per locus) identified by lo-siRF, respectively. Circle 7 displays the ChromHMM34 core-15 chromatin state for the LV, right ventricle (RV), right atrium (RA) and fetal heart (Fetal), using the standard color scheme (bottom right)34. Circle 8 presents a GWAS Manhattan plot (points, two-sided P < 0.05 from PLINK26), in which SNVs are color coded by their maximum r2 value relative to the 283 lo-siRF-prioritized SNVs. The outer heatmap layer represents LD-linked SNVs (r2 > 0.6) extracted from the FUMA reference panel, which lack GWAS P values. SNVs not in LD (r2 ≤ 0.6) with any of the 283 lo-siRF-prioritized SNVs appear in gray. The dashed line indicates GWAS P = 5 × 10−8. Circle 9 shows genes functionally mapped by FUMA. b, Pie charts depicting ANNOVAR enrichment results for the six lo-siRF loci (circle 2 in Fig. 3a and Table 1). The slice arc length represents the proportion of SNVs with a specific functional annotation. The slice radius indicates log2(E + 1), where E is the enrichment score computed as (proportion of SNVs with an annotation for a given locus)/(proportion of SNVs with an annotation relative to all available SNVs in the FUMA reference panel). The dashed circle indicates E = 1 (no enrichment). Asterisks denote two-sided Fisher’s exact test P values for the enrichment of each annotation. **P < 1 × 10−5; *P < 0.002. Details in Supplementary Data 4 and 5.
