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Research Paper

Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates

(Dr.) , , , , , , , , , & show all
Pages 664-673 | Received 19 May 2016, Accepted 30 Jun 2016, Published online: 25 Aug 2016

Figures & data

Table 1. Principal characteristics of the 736 participants of the California Childhood Leukemia study and CpG sites associated with maternal smoking during gestation.

Figure 1. Manhattan and quantile-quantile plots (QQ-plots) of the results of genome-wide associations tests looking at genome-wide associations between 3 candidate CpG sites sensitive to smoking [cg18146737 in the GFI1 gene on the chromosome 1 (panel A), cg05575921 in the AHRR gene on the chromosome 5 (panel B), and cg12803068 in the MYO1G gene on the chromosome 7 (panel C)] and genotype at 606,588 SNPs throughout the genome in 736 participants of the California Childhood Leukemia Study. The genomic inflation estimation factors lambda are reported on the plots. On the Manhattan plots, the red line corresponds to the canonical threshold of genome-wide significance [-log10(5 × 10−08)], and the blue line represents suggestive significance [-log10(10−05)].

Figure 1. Manhattan and quantile-quantile plots (QQ-plots) of the results of genome-wide associations tests looking at genome-wide associations between 3 candidate CpG sites sensitive to smoking [cg18146737 in the GFI1 gene on the chromosome 1 (panel A), cg05575921 in the AHRR gene on the chromosome 5 (panel B), and cg12803068 in the MYO1G gene on the chromosome 7 (panel C)] and genotype at 606,588 SNPs throughout the genome in 736 participants of the California Childhood Leukemia Study. The genomic inflation estimation factors lambda are reported on the plots. On the Manhattan plots, the red line corresponds to the canonical threshold of genome-wide significance [-log10(5 × 10−08)], and the blue line represents suggestive significance [-log10(10−05)].

Figure 2. Investigations of a ± 300 kb region around 3 CpG sites of interest (cg18146737, cg05575921, and cg12803068) for fine-mapping using imputed SNP data in 736 participants of the California Childhood Leukemia Study. The plots represent the P-values of the associations between DNA methylation at the CpG site of interest and genotype at the SNPs in the region. Canonical transcripts of the neighboring genes in the region are displayed based on the University of California, Santa Cruz Genome Browser data (hg19).Citation26 Linkage disequilibrium plots are represented below (r2 values) for SNPs that were genotyped on array. The blue line is located at the location of the CpG site of interest.

Figure 2. Investigations of a ± 300 kb region around 3 CpG sites of interest (cg18146737, cg05575921, and cg12803068) for fine-mapping using imputed SNP data in 736 participants of the California Childhood Leukemia Study. The plots represent the P-values of the associations between DNA methylation at the CpG site of interest and genotype at the SNPs in the region. Canonical transcripts of the neighboring genes in the region are displayed based on the University of California, Santa Cruz Genome Browser data (hg19).Citation26 Linkage disequilibrium plots are represented below (r2 values) for SNPs that were genotyped on array. The blue line is located at the location of the CpG site of interest.

Figure 2. (Continued).

Figure 2. (Continued).

Figure 2. (Continued).

Figure 2. (Continued).

Figure 3. Boxplots representing the association between DNA methylation at the 3 CpG sites of interest (cg18146737, cg05575921, and cg12803068) and exposure to maternal smoking during gestation, by genotype at the corresponding strongest associated SNP (rs141819830, rs148405299, and rs61087368) in 736 participants of the California Childhood Leukemia Study.

Figure 3. Boxplots representing the association between DNA methylation at the 3 CpG sites of interest (cg18146737, cg05575921, and cg12803068) and exposure to maternal smoking during gestation, by genotype at the corresponding strongest associated SNP (rs141819830, rs148405299, and rs61087368) in 736 participants of the California Childhood Leukemia Study.

Table 2. Tests of association between DNA methylation at the 3 CpG sites of interest and maternal smoking exposure during gestation while controlling (or not) for the genotype of the methylQTL (linear regression tests) in 736 participants of the California Childhood Leukemia Study.

Supplemental material

KEPI_A_1209614_supplementary_data.zip

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