Allele-specific transcription factor binding in liver and cervix cells unveils many likely drivers of GWAS signals.

Cavalli M, Pan G, Nord H, Wallén Arzt E, Wallerman O, Wadelius C

Genomics 107 (6) 248-254 [2016-06-00; online 2016-04-30]

Genome-wide association studies (GWAS) point to regions with associated genetic variants but rarely to a specific gene and therefore detailed knowledge regarding the genes contributing to complex traits and diseases remains elusive. The functional role of GWAS-SNPs is also affected by linkage disequilibrium with many variants on the same haplotype and sometimes in the same regulatory element almost equally likely to mediate the effect. Using ChIP-seq data on many transcription factors, we pinpointed genetic variants in HepG2 and HeLa-S3 cell lines which show a genome-wide significant difference in binding between alleles. We identified a collection of 3713 candidate functional regulatory variants many of which are likely drivers of GWAS signals or genetic difference in expression. A recent study investigated many variants before finding the functional ones at the GALNT2 locus, which we found in our genome-wide screen in HepG2. This illustrates the efficiency of our approach.

Bioinformatics Support for Computational Resources [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

National Genomics Infrastructure [Service]

PubMed 27126307

DOI 10.1016/j.ygeno.2016.04.006

Crossref 10.1016/j.ygeno.2016.04.006

pii: S0888-7543(16)30027-1