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We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci:\n                    <jats:italic>SSBP3<\/jats:italic>\n                    ,\n                    <jats:italic>THSD7A<\/jats:italic>\n                    ,\n                    <jats:italic>LAMB1<\/jats:italic>\n                    ,\n                    <jats:italic>PIDD1<\/jats:italic>\n                    ,\n                    <jats:italic>RORA<\/jats:italic>\n                    ,\n                    <jats:italic>HS3ST3B1<\/jats:italic>\n                    ,\n                    <jats:italic>LAMA5<\/jats:italic>\n                    , and\n                    <jats:italic>COL18A1<\/jats:italic>\n                    . We further confirm the\n                    <jats:italic>TCF4<\/jats:italic>\n                    locus in GWAS for admixed African and Hispanic\/Latino ancestries and show an enrichment of European-ancestry haplotypes at\n                    <jats:italic>TCF4<\/jats:italic>\n                    in FECD cases. Among the novel associations are low frequency missense variants in laminin genes\n                    <jats:italic>LAMA5<\/jats:italic>\n                    and\n                    <jats:italic>LAMB1<\/jats:italic>\n                    which, together with previously reported\n                    <jats:italic>LAMC1<\/jats:italic>\n                    , form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at\n                    <jats:italic>LAMA5<\/jats:italic>\n                    and\n                    <jats:italic>LAMB1<\/jats:italic>\n                    may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the\n                    <jats:italic>TCF4<\/jats:italic>\n                    CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.\n                  <\/jats:p>","DOI":"10.1038\/s42003-024-06046-3","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T09:01:54Z","timestamp":1712394114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-4672","authenticated-orcid":false,"given":"Bryan R.","family":"Gorman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1320-7161","authenticated-orcid":false,"given":"Michael","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cari L.","family":"Nealon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Halladay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalvi","family":"Duro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-6014","authenticated-orcid":false,"given":"Kyriacos","family":"Markianos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-5575","authenticated-orcid":false,"given":"Giulio","family":"Genovese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-2510","authenticated-orcid":false,"given":"Pirro G.","family":"Hysi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-8667","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Choquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie A.","family":"Afshari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4834","authenticated-orcid":false,"given":"Yi-Ju","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"VA Million Veteran Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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