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Genome-wide-association studies (GWAS) indicated potential CRF and disease genetics overlap. Here, we characterise 135 CRF loci following GWAS in 76029 UK Biobank participants. Enrichment of extra-cellular matrix gene-sets, genetic correlation with corneal thickness (70% (SE\u2009=\u20095%)), reported keratoconus risk variants at 13 loci, all support relevance to corneal stroma biology. Fine-mapping identifies a subset of 55 highly likely causal variants, 91% of which are non-coding. Genomic features enrichments, using all associated variants, also indicate prominent regulatory causal role. We newly established open chromatin landscapes in two widely-used human cornea immortalised cell lines using ATAC-seq. Variants associated with CRF were significantly enriched in regulatory regions from the corneal stroma-derived cell line and enrichment increases to over 5 fold for variants prioritised by fine-mapping-including at<jats:italic>GAS7, SMAD3<\/jats:italic>and<jats:italic>COL6A1<\/jats:italic>loci. Our analysis generates many hypotheses for future functional validation of aetiological mechanisms.<\/jats:p>","DOI":"10.1038\/s42003-020-01497-w","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T11:20:56Z","timestamp":1607685656000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Fine-mapping and cell-specific enrichment at corneal resistance factor loci prioritize candidate causal regulatory variants"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-6355","authenticated-orcid":false,"given":"Xinyi","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nefeli","family":"Dellepiane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2423-3090","authenticated-orcid":false,"given":"Erola","family":"Pairo-Castineira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4754-1675","authenticated-orcid":false,"given":"Thibaud","family":"Boutin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8371-2887","authenticated-orcid":false,"given":"Yatendra","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Bickmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-3797","authenticated-orcid":false,"given":"Veronique","family":"Vitart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"1497_CR1","doi-asserted-by":"publisher","first-page":"724546","DOI":"10.1155\/2014\/724546","volume":"2014","author":"N Garcia-Porta","year":"2014","unstructured":"Garcia-Porta, N. et al. 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