Additional file 1 of Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits

Additional file 1: Supplementary Figure 1. Global ancestry estimates by ADMIXTURE. 2,504 residents with African (AFR), East Asian (EAS), European (EUR), and South Asian (SAS) ancestry from the 1000 Genomes Project were used as the reference genotype panel to infer the super populations membership. Results were plotted for (A) samples in the Veterans Aging Cohort Study (VACS) cohort (n = 2244) with respect to reference samples, (B) a subset of the VACS cohort with admixed ancestral information (n = 105) with respect to reference samples. The reference and VACS samples were separated by the black line. Supplementary Figure 2. Inferred global ancestry of the VACS samples. Scatter plot of the genotype principal component analysis (PCA) results (PC1 and PC2) for the VACS cohort and 1000 Genome Project were plotted. The color indicated the super population of 1000 Genome reference samples (dots), and the inferred global ancestry of the VACS samples (triangles). Supplementary Figure 3. Selection of candidate CpGs associated with cocaine use in the Veterans Aging Cohort Study (VACS) samples. (A) Manhattan plot and (B) QQ plot (genomic inflation λ = 1.196) after meta-analysis to combine results from the 450K and EPIC cohorts. A total of 224 candidate CpG sites were identified. The red line indicates the p-value threshold used to identify candidate CU-associated CpG sites (p-value < 0.0001). Supplementary Figure 4. Two representative patterns of genetic effects by cocaine use for the meQTLs identified. (A-B): the distribution of methylation by the genotype among cocaine non-users and users. The patterns in the 450K cohort and EPIC cohort were plotted separately. (A) The genetic effect of rs13233191 on the methylation of cg17914838. (B) The genetic effect of rs7834638 on the methylation of cg21175976. CU: cocaine use; meQTL: methylation quantitative trait loci

Additional file 2 of Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits

Additional file 2: Supplementary Table 1. Candidate CpG sites for cocaine use after meta-analysis to combine results for the 450K and EPIC cohorts (Ntotal = 811). Supplementary Table 2. Selected SNP-CpG pairs (FDR < 0.05) after meta-analysis to combine results for the 450K and EPIC cohorts (Ntotal = 811) and clumping. Supplementary Table 3. Enriched Ingenuity Canonical Pathways identified using genes mapped by the meQTLs for cocaine-related DNA methylations. Supplementary Table 4. Significant traits associated with the top index meQTLs. A total of 60 studies reached the significance level after bonferroni correction (p < 1.7e-7), which consisted of 36 phenotypes (phenotype number). Supplementary Table 5. meQTLs trait enrichment using associates downloaded from GWAS Catalog ( https://www.ebi.ac.uk/gwas/ ). MeQTLs for cocaine-related DNA methylations were used. Supplementary Table 6. Candidate CpG sites for cocaine use frequency (high frequency users VS low frequency users). Supplementary Table 7. MeQTLs (FDR < 0.05) for cocaine use frequency-related DNA methylations after meta-analysis to combine results for the 450K and EPIC cohorts (Ntotal = 293) and clumping. Supplementary Table 8.  Enriched Ingenuity Canonical Pathways identified using genes mapped by the meQTLs for cocaine use frequency-related DNA methylations. Supplementary Table 9. Significant traits associated with the top index meQTLs for cocaine use frequency-related DNA methylations. A total of 4 studies reached the significance level after bonferroni correction (p < 7.0e-7), which consisted of 4 phenotypes (phenotype number). Supplementary Table 10. meQTLs trait enrichment using associates downloaded from GWAS Catalog ( https://www.ebi.ac.uk/gwas/ ). MeQTLs for cocaine use frequency-related DNA methylations were used

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects