File S1 - New Variants Including ARG1 Polymorphisms Associated with C-Reactive Protein Levels Identified by Genome-Wide Association and Pathway Analysis

Figure S1, A Quantile–Quantile plot of P-values in the GWAS for serum CRP levels (Stage 1). The horizontal axis indicates the expected -log10 (P-values). The vertical axis indicates the observed -log10 (P-values). The red line represents y = x. Figure S2, (A) Stage 1 data showing a regional association (upper panel) and linkage disequilibrium (LD; lower panel) plots of the CRP locus around rs7553007. Arrow head represents rs7553007. (B) Stage 1 data showing a regional association (upper panel) and linkage disequilibrium (LD; lower panel) plots of the HNF1A locus around rs2393791. Arrow head represents rs2393791. Figure S3, Pairwise linkage disequilibrium (LD) between the selected SNPs in ARG1 locus around rs9375813. LD plots for Korea population were drawn using the genotype data from the present study, whereas LD plots for Japanese, Chinese, Europeans and Africans were made from genotype data from HapMap Stage 2. Blue ID indicates the most significant SNP. Purple ID indicates the SNPs whose rank got elevated after re-prioritization. Figure S4, Gene network of photoreceptor outer segment pathway by GeneMANIA analysis. Using the genes identified from pathway analysis, GeneMANIA network analysis was performed. Query genes are depicted as black nodes and discovered genes are depicted as gray nodes. Edges show different interactions among genes; purple indicates for co-expression; light-blue indicates for pathway; dark yellow indicates for shared protein domains; red indicates for physical interactions; dark blue indicates for co-localization; green indicates for genetic interactions. Node sizes are determined according to their weight in the network. Figure S5, Gene network of cell surface binding pathway by GeneMANIA. Figure S6, Gene network of cholesterol binding pathway by GeneMANIA. Figure S7, Gene network of bacterial cell surface binding pathway by GeneMANIA. Table S1, Characteristics of the subjects in stage 1 and 2 data. The stage 1 consists of 7,626 unrelated Korean subjects (3,586 men and 4,040 women) and the stage 2 consists of 903 Korean individuals (518 male and 385 female). Table S2, SNP loci associated with serum CRP levels in the stage 1 data. Table S3, SNP loci associated with serum CRP levels in the stage 2 data and meta-analysis. Table S4, P-values and LD values of neighboring SNPs of the rs9375813 in the ARG1 locus. Table S5, Associations of the previously reported CRP-related loci. Based on genotyped and imputed SNP data, we observed the associations of previously reported CRP-associated loci. Table S6, Re-prioritized genetic variants list after GWAS. Table S7, Associations of the top significant SNP polymorphisms on cardiovascular disease traits based on the whole KARE samples (7,626 samples). Table S8, Genes mapped with variant in adaptive immune response. We performed a pathway analysis to identify more variants and pathways that may influence CRP levels using ICSNPathway software and reconfirmed the identified pathways with GSA-SNP software. This table shows the genes mapped with variants in adaptive immune response among the ten candidate pathways enriched with CRP-associated SNPs in ICSNPathay analysis. Table S9, Genes mapped with variant in leukocyte mediated immunity. Table S10, Genes mapped with variant in photoreceptor outer segment. Table S11, Genes mapped with variant in cell surface binding. Table S12, Genes mapped with variant in cholesterol binding. Table S13, Genes mapped with variant in bacterial cell surface binding. Table S14, Pathway analysis results of GSA-SNP software. Table S15, Combined P value estimation of ICSNPathway and GSA-SNP by Fisher Statistics. (PDF)