Genetic Variants Associated with Supernormal Coronary Arteries

Figures

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  Supplemental Fig.1.. Enrollment of the study population

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  Fig.1. Manhattan plot of the genome-wide association study (GWAS) results. (A) A Manhattan plot [−log10(p)] for supernormal coronary arteries is shown. The red horizontal line corresponds to the threshold for suggestive significance (p=5×10−5), and blue dots denote significant loci according to GWAS findings. The nearest genes to the top variants are shown over each locus. Genes showing significant expression quantitative trait loci associations are in green. (B) Genotypes of lead single-nucleotide polymorphisms (y axis) in study participants (x axis) are shown. The color of each tile represents the number of affected alleles related to supernormal coronary arteries.

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  Supplemental Fig.2. PCA of the genetic variants. The first three PCs of genetic ancestry are presented as the mean±3 SD (blue dashed lines) and the mean±5 SD of each PC (red lines). Each dot represents a participant in the study. Red circles, green X dots, and blue X dots represent the control from CGC cohort, supernormal from CGC cohort, and supernormal from CMERC-HI cohort, respectively. Abbreviations: CGC, Cardiovascular Genome Center; CMERC-HI, Cardiovascular and Metabolic Disease Etiology Research Center - High Risk

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  Supplemental Fig.3. Quantile–quantile plot of GWAS results. Quantile–quantile plot of GWAS results. The negative logarithm of the observed (Y-axis) and expected (X-axis) P-values are plotted for each SNP. The red line indicates the null hypothesis of no true association (y=x), and the grey region indicates the 95% confidence interval of the red line. The genomic inflation factor (λGC) is shown on the upper left.

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  Supplemental Fig.4. Regional plots of loci surrounding top variants. Regional plots of −log10(P) are presented for the loci associated with 3 the supernormal coronary arteries. The results of association analysis are shown in the 2-Mbp region surrounding the top variant (purple). Each 4 dot indicates a variant, and different colors represent the linkage disequilibrium (r2) of each variant from the top variant.

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  Supplemental Fig.5. Effective allele frequency of lead variants by cohort. The effective allele frequency of lead variants are presented for each group and cohort. Red, dark blue, green, and light blue bars represent the effective allele frequency in the control group, supernormal group (CGC＋CMERC-HI), supernormal group from the CGC cohort, and supernormal group from the CMERC-HI cohort, respectively. Standard deviation of the effective allele frequency in two supernormal cohorts are presented as error bar. Abbreviations: CGC, Cardiovascular Genome Center; CMERC-HI, Cardiovascular and Metabolic Disease Etiology Research Center - High Risk.

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  Fig.2. Expression quantitative trait loci (eQTL) results from the Genotype-Tissue Expression (GTEx). The figure shows violin plots of normalized gene expression levels (y axis) of GTEx project participants according to genotypes of genome-wide association study (GWAS) lead variants (x axis) at eQTL in the coronary artery, whole blood, or adipose tissues. The p value and normalized effect size (NES) of eQTL analysis from the GTEx data are presented above each violin plot. Numbers of participants according to genotype from GTEx data are presented below the genotype.

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  Fig.3.. Plausible biological links of several genes near the lead variants to athero-protection