Fig. 5: The shared genetic etiology for CAD, AF, and AS conditioned on SBP, TG, and LDL-C at the CASZ1 locus.

A Prioritizing DNA methylation sites at the CASZ1 locus for CAD, AF, and AS conditioned on SBP, TG and LDL-C. The top two tracks show the −log₁₀(P) of the GWAS SNPs for vascular diseases (CAD (in orange), AF (in red) and AS (in green)) and related risk factors (SBP (in red), TG (in purple), LDL-C (in blue)), respectively. The next two tracks show −log10(P) of SNP associations for DNA methylation sites (cg12760995 and cg15622917) with OPERA marginal PPA > 0.9 and P-HEIDI > 0.01 (see the “Methods” section). The subsequent track shows the gene name and size of the flanking region within 500 kb of the 10.8 MB on chromosome 1. The track on the bottom shows 14 chromatin state annotations inferred from the 127 Roadmap Epigenomics Mapping Consortium samples at the 10.6 Mb to 11.0 Mb position of chromosome 1. B LD pattern of GWAS SNPs for CAD, AF, AS, SBP, TG, and LDL-C at the CASZ1 locus. The top six tracks show the −log₁₀(P) of the GWAS SNPs for vascular diseases (CAD, AF, and AS) and related risk factors (SBP, TG, LDL-C) within 10 kb of the 10.8 MB on chromosome 1. In each single track, the red diamond with a black border represents the index SNP with the most strongly association in the region, and dots of different colors represent different LD scores with the index SNP. The track on the bottom shows LD heatmap, and the triangles with black borders represent the identified blocks defined by Gabriel et al.⁴⁶. CAD coronary artery disease, AF Atrial fibrillation, SBP systolic blood pressure, TG total triglyceride, LDL-C low-density lipoprotein cholesterol.