Research Papers:

Polymorphisms involving gain or loss of CpG sites are significantly enriched in trait-associated SNPs

Dan Zhou _, Zhenli Li, Dan Yu, Ledong Wan, Yimin Zhu, Maode Lai and Dandan Zhang

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Oncotarget. 2015; 6:39995-40004. https://doi.org/10.18632/oncotarget.5650

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Dan Zhou1,2,3, Zhenli Li1,2, Dan Yu1,2, Ledong Wan1,2, Yimin Zhu3, Maode Lai1,2, Dandan Zhang1,2

1Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China

2Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China

3Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, 310058, China

Correspondence to:

Dandan Zhang, e-mail: [email protected]

Maode Lai, e-mail: [email protected]

Keywords: epigenetic, DNA methylation, cancer, single nucleotide polymorphism (SNP), CpG site

Received: July 01, 2015     Accepted: October 02, 2015     Published: October 14, 2015


Some single nucleotide polymorphisms (SNPs) influence the existence of CpG sites, the basis of DNA modification such as methylation and hydroxymethylation. These polymorphisms can lead to gain or loss of CpG sites and were defined as CpG site related SNPs (cgSNPs) in this study. The cgSNPs change DNA sequence and might potentially affect DNA modification such as methylation. However, the functional consequence of cgSNPs is poorly understood. We observed that a considerable proportion (23.0%) of common variants were cgSNPs in human genome. Mutations involving loss of CpG sites were associated with reduced levels of methylation (~20.2%) using The Cancer Genome Atlas (TCGA) data. Using public databases (SCAN and seeQTL) of expression quantitative trait loci (eQTLs), we found that the cgSNPs were significantly enriched in eQTLs via logistic regression and simulation test. Furthermore, we observed that cgSNPs were more likely to be trait-associated loci especially cancers using a catalog of published genome-wide association studies (GWAS) recorded by National Human Genome Research Institute (NHGRI). Our results indicated that cgSNP might be meaningful as annotation either in SNP functional prediction or in screening for trait-associated SNPs.

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