{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T01:28:01Z","timestamp":1768613281298,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,12]]},"group-title":"Genetic and Genomic Medicine","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Variation in the elastin gene (\n                  <jats:italic>ELN<\/jats:italic>\n                  ) may contribute to connective tissue disease beyond the known disease associations of Supravalvar Aortic Stenosis and Cutis Laxa. Exome data from MyCode Community Health Initiative participants were analyzed for\n                  <jats:italic>ELN<\/jats:italic>\n                  rare variants (mean allele frequency &lt;1%, not currently annotated as benign). Participants with variants of interest underwent phenotyping by dual chart review using a standardized abstraction tool. Additionally, all rare variants that met inclusion criteria were collapsed into an\n                  <jats:italic>ELN<\/jats:italic>\n                  gene burden score to perform a Phenome-wide Association Study (PheWAS). Two hundred and ninety-six eligible participants with relevant\n                  <jats:italic>ELN<\/jats:italic>\n                  variants were identified from 184,293 MyCode participants. One hundred and three of 254 living participants (41%) met phenotypic criteria, most commonly aortic hypoplasia, arterial dilation, aneurysm, and dissection, and connective tissue abnormalities.\n                  <jats:italic>ELN<\/jats:italic>\n                  variation was significantly (P &lt;2.8\u00d710\n                  <jats:sup>\u22125<\/jats:sup>\n                  ) associated with \u201carterial dissection\u201d in the PheWAS and two connective tissue Phecodes approached significance. Variation in\n                  <jats:italic>ELN<\/jats:italic>\n                  is associated with connective tissue pathology beyond classic phenotypes.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>eTOC Blurb<\/jats:title>\n                  <jats:p>\n                    Carriers of variants of interest in the elastin gene (\n                    <jats:italic>ELN<\/jats:italic>\n                    ) were evaluated for presence of findings that could be associated with the variation. Chart review and Phenome-wide Association Studies were used. Results are consistent with variation in\n                    <jats:italic>ELN<\/jats:italic>\n                    being associated with findings affecting elastic tissues beyond classic phenotypes.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.10.24313340","type":"posted-content","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T18:10:47Z","timestamp":1726164647000},"source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic Findings Associated with Variation in Elastin"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-8712","authenticated-orcid":false,"given":"Anne","family":"Justice","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa 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