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Curr Opin Genet Dev DOI:10.1016/j.gde.2013.10.009

Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.

Publication TypeJournal Article
Year of Publication2013
AuthorsTrynka, G, Raychaudhuri, S
JournalCurr Opin Genet Dev
Date Published2013 Dec
KeywordsAlleles, Chromatin, Chromosome Mapping, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide

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.


Alternate JournalCurr. Opin. Genet. Dev.
PubMed ID24287333
PubMed Central IDPMC4073234
Grant ListU01 HG007033 / HG / NHGRI NIH HHS / United States
K08AR055688 / AR / NIAMS NIH HHS / United States
1R01AR063759-01A1 / AR / NIAMS NIH HHS / United States
U01 GM092691 / GM / NIGMS NIH HHS / United States
5U01GM092691-04 / GM / NIGMS NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
U01HG0070033 / HG / NHGRI NIH HHS / United States
K08 AR055688 / AR / NIAMS NIH HHS / United States