baal-nf identifies motif-disrupting variants that decrease transcription factor binding affinity
Human traits vary in part due to genetically-determined change of transcription factor (TF) binding affinity within gene regulatory regions. However, few trait-causal variants or mechanisms are known. Here we propose 1,960 variants as strong candidates for causally altering human traits. They were discovered by baal-nf which uses ChIP-sequencing data to identify allelic imbalance at heterozygous sites ( allele-specific binding sites; ASBs) within affinity-concordant positions within TF- and/or co-factor binding motifs. These variants are evolutionarily conserved, and enriched for trait associations and gene expression QTLs. baal-nf and these high-quality ASBs now allow trait variation due to altered TF binding to be investigated.
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