Identifying causal regulatory SNPs in ChIP-seq enhancers

Di Huang, Ivan Ovcharenko
2014 Nucleic Acids Research  
Thousands of non-coding SNPs have been linked to human diseases in the past. The identification of causal alleles within this pool of disease-associated non-coding SNPs is largely impossible due to the inability to accurately quantify the impact of noncoding variation. To overcome this challenge, we developed a computational model that uses ChIP-seq intensity variation in response to non-coding allelic change as a proxy to the quantification of the biological role of non-coding SNPs. We applied
more » ... this model to HepG2 enhancers and detected 4796 enhancer SNPs capable of disrupting enhancer activity upon allelic change. These SNPs are significantly over-represented in the binding sites of HNF4 and FOXA families of liver transcription factors and liver eQTLs. In addition, these SNPs are strongly associated with liver GWAS traits, including type I diabetes, and are linked to the abnormal levels of HDL and LDL cholesterol. Our model is directly applicable to any enhancer set for mapping causal regulatory SNPs.
doi:10.1093/nar/gku1318 pmid:25520196 pmcid:PMC4288203 fatcat:x6s5eugwkrgmrhksv2piaeqina