Sep 29, 2017

Identification of breast cancer associated variants that modulate transcription factor binding

PLoS Genetics
Yunxian LiuMichael J Guertin


Genome-wide association studies (GWAS) have discovered thousands loci associated with disease risk and quantitative traits, yet most of the variants responsible for risk remain uncharacterized. The majority of GWAS-identified loci are enriched for non-coding single-nucleotide polymorphisms (SNPs) and defining the molecular mechanism of risk is challenging. Many non-coding causal SNPs are hypothesized to alter transcription factor (TF) binding sites as the mechanism by which they affect organismal phenotypes. We employed an integrative genomics approach to identify candidate TF binding motifs that confer breast cancer-specific phenotypes identified by GWAS. We performed de novo motif analysis of regulatory elements, analyzed evolutionary conservation of identified motifs, and assayed TF footprinting data to identify sequence elements that recruit TFs and maintain chromatin landscape in breast cancer-relevant tissue and cell lines. We identified candidate causal SNPs that are predicted to alter TF binding within breast cancer-relevant regulatory regions that are in strong linkage disequilibrium with significantly associated GWAS SNPs. We confirm that the TFs bind with predicted allele-specific preferences using CTCF ChIP-seq data...Continue Reading

  • References73
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  • References73
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Mentioned in this Paper

Genome-Wide Association Study
ANKLE1 gene
Gene Expression Regulation, Neoplastic
Quantitative Trait Loci
Dysequilibrium Syndrome
Breast Tissue Sample

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