title: Allele-specific transcription factor binding in liver and cervix cells unveils many likely drivers of GWAS signals.
abstract: 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.
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Cavalli
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Gang
authors.initials: G
authors.lastname: Pan
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Nord
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Emelie
authors.initials: E
authors.lastname: Wallén Arzt
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Wallerman
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Electronic address: claes.wadelius@igp.uu.se.
authors.forename: Claes
authors.initials: C
authors.lastname: Wadelius
mesh_terms: D000483:Alleles; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D015810:Linkage Disequilibrium; D008099:Liver / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D017350:N-Acetylgalactosaminyltransferases; D014157:Transcription Factors; D000097763:Polypeptide N-acetylgalactosaminyltransferase
keywords: Allele-specific regulation; Association to GWAS/eQTLs; Functional variants