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.

SUBMITTER: Trynka G 

PROVIDER: S-EPMC4073234 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature