Haplotype of CpG related SNPs is associated with DNA methylation pattern. Y. Ma1, C. E. Smith1, Y. C. Lee1, L. D. Parnell1, C. Q. Lai1, J. M. Ordovas1,2,3 1) Nutritional Genomics, Jean Mayer USDA-HNRCA at Tufts University, Boston, MA; 2) Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain; 3) Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain.

   Background: DNA methylation occurs on CpG dinucleotides. Single nucleotide polymorphisms (SNPs) may affect DNA methylation by changing the formation of CpG dinucleotides. In this study, we defined those SNPs which could change the formation of CpG dinucleotides as CpG related SNPs (CGS). Each CGS has two types of alleles, which can either create or disrupt CpG dinucleotides. The condition when an individual carries the allele to create CpG dinucleotide is called CGS-C, while the condition when an individual carries the allele to disrupt CpG dinucleotide is called CGS-D. Methods: We applied a genome-wide scale and integrated bioinformatics analysis to publicly available datasets of both genotypes (HapMap project) and methylation patterns in B lymphocyte cell line (ENCODE project) to explore the relationship between these CGSs and DNA methylation from three perspectives: (1) whether the genotype of a single CGS affects the DNA methylation of that locus; (2) whether two CGSs in high linkage disequilibrium (LD) tend to be with the same type of allele (create or disrupt the CpG); (3) whether the haplotype consisting of multiple CGSs in high LD is associated with DNA methylation pattern of that region. Results: About 80% of CGS-Cs can be methylated. In addition, when two CGSs are in high LD, they tend to act as the same type of allele, which means that if the allele of one CGS is to create the CpG then the allele of another CGS in high LD tend to create the CpG also. This finding is highly consistent in both unrelated individuals and family members of HapMap CEU population. Finally, the haplotype of one LD block, consisting of multiple CGSs close to both CpG islands and promoter regions, is correlated with DNA methylation pattern according to both categorical and continuous analysis. Conclusion: CGSs which are close to CpG islands and promoters may affect DNA methylation pattern in the form of haplotype.

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