title: Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.
abstract: While studies to associate genomic variants to complex traits have gradually become increasingly productive, the molecular mechanisms that underlie these associations are rarely understood. Because only a small fraction of trait-associated variants can be linked to coding sequences, investigators have speculated that many of the underlying causal alleles influence non-coding gene regulatory sites. Recent studies have successfully identified examples of mechanisms for non-coding alleles at individual loci. Now, genome-wide chromatin assays have resulted in maps of dozens of genomic annotations of the non-coding genome across multiple different tissues, cell types and cell lines. This gives a tremendous opportunity to integrate these annotations with complex trait signals to globally interpret associated variants, and prioritize likely causal alleles. Here, we review the examples of mechanisms by which non-coding, common alleles result in phenotypes. We discuss the efforts to integrate common trait-associated variants with genomic annotations. Finally, we highlight some caveats of these approaches and outline future directions for improvement.
authors.affiliation: Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Partners Center for Personalized Genetic Medicine, Boston, MA, USA.
authors.forename: Gosia
authors.initials: G
authors.lastname: Trynka
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
mesh_terms: D000483:Alleles; D002843:Chromatin / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D002843:Chromatin