RT Journal Article SR Electronic T1 GARFIELD - GWAS Analysis of Regulatory or Functional Information Enrichment with LD correction JF bioRxiv FD Cold Spring Harbor Laboratory SP 085738 DO 10.1101/085738 A1 Valentina Iotchkova A1 Graham R.S. Ritchie A1 Matthias Geihs A1 Sandro Morganella A1 Josine L. Min A1 Klaudia Walter A1 Nicholas Timpson A1 UK10K Consortium A1 Ian Dunham A1 Ewan Birney A1 Nicole Soranzo YR 2016 UL http://biorxiv.org/content/early/2016/11/07/085738.abstract AB Loci discovered by genome-wide association studies (GWAS) predominantly map outside protein-coding genes. The interpretation of 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 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 GWAS 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 that current methods do not offer. We further assess enrichment statistics for 27 GWAS traits within regulatory regions from the ENCODE and Roadmap projects. We characterise unique enrichment patterns for traits and annotations, driving novel biological insights. The method is implemented in standalone software and R package to facilitate its application by the research community.