Abstract:
:Loci discovered by genome-wide association studies predominantly map outside protein-coding genes. The interpretation of the functional consequences of non-coding variants can be greatly enhanced by catalogs of regulatory genomic regions in cell lines and primary tissues. However, robust and readily applicable methods are still lacking by which to systematically evaluate the contribution of these regions to genetic variation implicated in diseases or quantitative traits. Here we propose a novel approach that leverages genome-wide association studies' findings with regulatory or functional annotations to classify features relevant to a phenotype of interest. Within our framework, we account for major sources of confounding not offered by current methods. We further assess enrichment of genome-wide association studies for 19 traits within Encyclopedia of DNA Elements- and Roadmap-derived regulatory regions. We characterize unique enrichment patterns for traits and annotations driving novel biological insights. The method is implemented in standalone software and an R package, to facilitate its application by the research community.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Iotchkova V,Ritchie GRS,Geihs M,Morganella S,Min JL,Walter K,Timpson NJ,UK10K Consortium.,Dunham I,Birney E,Soranzo Ndoi
10.1038/s41588-018-0322-6subject
Has Abstractpub_date
2019-02-01 00:00:00pages
343-353issue
2eissn
1061-4036issn
1546-1718pii
10.1038/s41588-018-0322-6journal_volume
51pub_type
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