Functional annotation and eQTL analysis

Functional prediction of the identified SNPs was performed by using three online tools: SNPinfo (https://snpinfo.niehs.nih.gov/snpinfo/snpfunc.htm), RegulomeDB (http://www.regulomedb.org/), and HaploReg (http://archive.broadinstitute.org/mammals/haploreg/haploreg.php). SNPinfo is a website with a sute of tools for single nucleotide polymorphism detection; RegulomeDB is a website that allows one to identify DNA features and regulatory elements in non-coding regions of the human genome; and HaploReg is a tool for exploring annotations of the noncoding genome at variants on haplotype blocks, such as candidate regulatory SNPs at disease-associated loci.

We performed the expression quantitative trait loci (eQTL) analysis to investigate the correlations between genotypes of the identified SNPs and mRNA expression levels of the corresponding genes. Data from other three sources were also used, including the 1000 Genomes Project, the Cancer Genome Atlas (TCGA) (http://tcga-data.nci.gov/tcga/), and the Genotype-Tissue Expression project (GTEx). In the 1000 Genomes Project, the mRNA expression data were from the lymphoblastoid cell lines of 373 Europeans. In the TCGA, there were genotype and phenotype data for 127 Europeans, while GTEx was an online database of 663 samples with various genotype and gene expression data from different tissues. Additionally, Oncomine™ database was used to compare mRNA expression levels between normal and tumor tissues (https://www.oncomine.org/).