Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.
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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. |
Year of Publication | 2013
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Journal | Curr Opin Genet Dev
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Volume | 23
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Issue | 6
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Pages | 635-41
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Date Published | 2013 Dec
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ISSN | 1879-0380
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URL | |
DOI | 10.1016/j.gde.2013.10.009
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PubMed ID | 24287333
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PubMed Central ID | PMC4073234
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Grant list | U01 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
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