{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:57Z","timestamp":1792790397946,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,22]]},"group-title":"Cardiovascular Medicine","reference-count":94,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Heart Lung and Blood Institute","award":["K08HL173697"],"award-info":[{"award-number":["K08HL173697"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Heart Lung and Blood Institute","award":["R01HL109942"],"award-info":[{"award-number":["R01HL109942"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Heart Association","award":["23POST1011251"],"award-info":[{"award-number":["23POST1011251"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Remebrin\u2019 Benjamin"},{"name":"John Ritter Foundation"},{"name":"National Human Genome Research Institute","award":["U01HG011744"],"award-info":[{"award-number":["U01HG011744"]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Human Genome Research Institute","award":["U24HG011746"],"award-info":[{"award-number":["U24HG011746"]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Center for Advancing Translational Sciences","award":["UL1TR001878"],"award-info":[{"award-number":["UL1TR001878"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"crossref"}]},{"name":"VA Merit Award","award":["I01BX003362"],"award-info":[{"award-number":["I01BX003362"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Thoracic aortic aneurysms enlarge silently and can cause fatal aortic dissection without timely surgical repair, underscoring the need for improved approaches to identify individuals at high risk. Rare pathogenic variants in established heritable thoracic aortic disease (HTAD) genes explain only a subset of familial and fewer nonfamilial thoracic aortic disease (TAD) cases.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed phenotype-stratified, genome-wide, gene-based rare-variant burden analyses of ultrarare damaging missense and predicted loss-of-function variants. Primary analyses focused on aortic dissection, thoracic aortic aneurysm requiring surgical repair, and their combined phenotype. Broader thoracic aortic aneurysm (TAA) was evaluated as a secondary phenotype. Discovery analyses were conducted in the UK Biobank and All of Us, followed by independent replication in the Penn Medicine BioBank, Mass General Brigham Biobank, and Million Veteran Program. Discovery and replication results were subsequently combined in an overall fixed-effect, inverse-variance-weighted meta-analysis across up to five biobanks. Implicated genes were further evaluated in additional clinically ascertained TAD cohorts and using single-cell transcriptomic data from human thoracic aortic tissue.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Discovery analyses identified 80 genes reaching study-wide significance across the prespecified TAD phenotypes. These included six established and two putative HTAD genes. Fourteen genes demonstrated independent replication support and reached study-wide significance in the overall meta-analysis across up to five biobanks, which included more than 10,000 cases and 880,000 controls. The eight novel candidate genes among these were\n                    <jats:italic>FNDC3B, ROCK1, URM1, SLFN11, ENPP1, CLEC16A, CREM,<\/jats:italic>\n                    and\n                    <jats:italic>VCAN<\/jats:italic>\n                    . Associations were strongest for dissection and TAA requiring surgical repair. Four novel associations were driven exclusively by missense variants.\n                    <jats:italic>FNDC3B<\/jats:italic>\n                    was observed in a family with HTAD, while additional variants were identified primarily in sporadic dissection or aortic surgery cohorts, suggesting that other genetic or physiologic factors may influence penetrance. The implicated genes showed cell-type-specific expression patterns in human thoracic aortic tissue.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings expand the genetic architecture of TAD by identifying eight novel candidate genes and demonstrate the utility of phenotype-stratified rare variant burden analyses across large biobanks for gene discovery.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.16.26363254","type":"posted-content","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:05:16Z","timestamp":1790103916000},"source":"Crossref","is-referenced-by-count":0,"title":["Gene-Based Rare Variant Burden Analyses Across Biobanks Identify Novel High-Risk Genes for Thoracic Aortic Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8536-3091","authenticated-orcid":false,"given":"David R.","family":"Murdock","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pujun","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongchuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Bermudez","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"DePaolo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Cabot","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaiya","family":"Nazeen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"},{"name":"Division of Genetics, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habib","family":"Nasir","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat M.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok","family":"Jha","sequence":"additional","affiliation":[{"name":"Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Elefteriades","sequence":"additional","affiliation":[{"name":"Aortic Institute at Yale-New Haven Hospital, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobbi","family":"McGivern","sequence":"additional","affiliation":[{"name":"GeneDx, LLC, Gaithersburg, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"McWalter","sequence":"additional","affiliation":[{"name":"GeneDx, LLC, Gaithersburg, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha K.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Lynch","sequence":"additional","affiliation":[{"name":"VA Informatics and Computing Infrastructure (VINCI), Salt Lake City VA, Salt Lake City, UT, USA"},{"name":"Department of Internal Medicine, Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong-Mi","family":"Chang","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA"},{"name":"Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Tsao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"VA Palo Alto Health Care System, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"VA Million Veteran Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Penn Medicine BioBank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Damrauer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092504251615000_2026.09.16.26363254v1.1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001412"},{"key":"2026092504251615000_2026.09.16.26363254v1.2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001106"},{"key":"2026092504251615000_2026.09.16.26363254v1.3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.702720"},{"key":"2026092504251615000_2026.09.16.26363254v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01420-z"},{"key":"2026092504251615000_2026.09.16.26363254v1.5","first-page":"203","article-title":"Update on the genetic risk for thoracic aortic aneurysms and acute aortic dissections: implications for clinical care","volume":"62","year":"2021","journal-title":"J. Cardiovasc. Surg"},{"key":"2026092504251615000_2026.09.16.26363254v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.089"},{"key":"2026092504251615000_2026.09.16.26363254v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaf926"},{"key":"2026092504251615000_2026.09.16.26363254v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02140-2"},{"key":"2026092504251615000_2026.09.16.26363254v1.9","first-page":"28","article-title":"A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: a cohort allelic sums test (CAST)","volume":"615","year":"2006","journal-title":"Mutat. Res"},{"key":"2026092504251615000_2026.09.16.26363254v1.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000384"},{"key":"2026092504251615000_2026.09.16.26363254v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01966-6"},{"key":"2026092504251615000_2026.09.16.26363254v1.12","doi-asserted-by":"crossref","first-page":"115355","DOI":"10.1016\/j.celrep.2025.115355","article-title":"Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson\u2019s disease","volume":"44","year":"2025","journal-title":"Cell Rep"},{"key":"2026092504251615000_2026.09.16.26363254v1.13","doi-asserted-by":"crossref","unstructured":"DePaolo J , Guo D-C , Murdock DR , Cecchi AC , LeMaire SA , Shen HY , Estrera AL , Safi HJ , Coselli JS , Smith J , et al. Employing bioinformatic tools to identify high-risk variants of uncertain significance in aortopathy genes that increase aortic dissection risk. Genet. Med. 2026;102571.","DOI":"10.1016\/j.gim.2026.102571"},{"key":"2026092504251615000_2026.09.16.26363254v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2026092504251615000_2026.09.16.26363254v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"2026092504251615000_2026.09.16.26363254v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"2026092504251615000_2026.09.16.26363254v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"2026092504251615000_2026.09.16.26363254v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06957-x"},{"key":"2026092504251615000_2026.09.16.26363254v1.19","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.3390\/jpm12121974","article-title":"The Penn Medicine BioBank: Towards a genomics-enabled learning healthcare system to accelerate precision medicine in a diverse population","volume":"12","year":"2022","journal-title":"J. Pers. Med"},{"key":"2026092504251615000_2026.09.16.26363254v1.20","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.3390\/jpm12081323","article-title":"The evolution of a large Biobank at mass general Brigham","volume":"12","year":"2022","journal-title":"J. Pers. Med"},{"key":"2026092504251615000_2026.09.16.26363254v1.21","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/80.1.27"},{"key":"2026092504251615000_2026.09.16.26363254v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"2026092504251615000_2026.09.16.26363254v1.23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/jrsm.12","article-title":"A basic introduction to fixed-effect and random-effects models for meta-analysis","volume":"1","year":"2010","journal-title":"Res. Synth. Methods"},{"key":"2026092504251615000_2026.09.16.26363254v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2015.09.002"},{"key":"2026092504251615000_2026.09.16.26363254v1.25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41572-021-00298-7","article-title":"Marfan syndrome","volume":"7","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2026092504251615000_2026.09.16.26363254v1.26","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2016-310631"},{"key":"2026092504251615000_2026.09.16.26363254v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.6"},{"key":"2026092504251615000_2026.09.16.26363254v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.04.007"},{"key":"2026092504251615000_2026.09.16.26363254v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"2026092504251615000_2026.09.16.26363254v1.30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421001"},{"key":"2026092504251615000_2026.09.16.26363254v1.31","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307130"},{"key":"2026092504251615000_2026.09.16.26363254v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.03.002"},{"key":"2026092504251615000_2026.09.16.26363254v1.33","doi-asserted-by":"publisher","DOI":"10.1086\/512821"},{"key":"2026092504251615000_2026.09.16.26363254v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3475"},{"key":"2026092504251615000_2026.09.16.26363254v1.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006916"},{"key":"2026092504251615000_2026.09.16.26363254v1.36","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046528"},{"key":"2026092504251615000_2026.09.16.26363254v1.37","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3390\/biom13020399","article-title":"Single-cell RNA-seq analysis reveals macrophages are involved in the pathogenesis of human sporadic acute type A aortic dissection","volume":"13","year":"2023","journal-title":"Biomolecules"},{"key":"2026092504251615000_2026.09.16.26363254v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0038-0"},{"key":"2026092504251615000_2026.09.16.26363254v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.06.019"},{"key":"2026092504251615000_2026.09.16.26363254v1.40","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm201"},{"key":"2026092504251615000_2026.09.16.26363254v1.41","first-page":"103","article-title":"Epidemiology of thoracic aortic dissection","volume":"8","year":"2010","journal-title":"Nat. Rev. Cardiol"},{"key":"2026092504251615000_2026.09.16.26363254v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.029"},{"key":"2026092504251615000_2026.09.16.26363254v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.007"},{"key":"2026092504251615000_2026.09.16.26363254v1.44","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1038\/s41588-025-02403-y","article-title":"Scalable and accurate rare variant meta-analysis with Meta-SAIGE","volume":"57","year":"2025","journal-title":"Nat. Genet"},{"key":"2026092504251615000_2026.09.16.26363254v1.45","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.037661"},{"key":"2026092504251615000_2026.09.16.26363254v1.46","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.035070"},{"key":"2026092504251615000_2026.09.16.26363254v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.09.062"},{"key":"2026092504251615000_2026.09.16.26363254v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.05.077"},{"key":"2026092504251615000_2026.09.16.26363254v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"2026092504251615000_2026.09.16.26363254v1.50","doi-asserted-by":"crossref","first-page":"119935","DOI":"10.1016\/j.bbamcr.2025.119935","article-title":"Silencing of fibronectin type III domain-containing protein 3A (FNDC3A) attenuates epithelial-to-mesenchymal transition (EMT), cancer invasion, and stemness in triple-negative breast cancer (TNBC)","volume":"1872","year":"2025","journal-title":"Biochim. Biophys. Acta Mol. Cell Res"},{"key":"2026092504251615000_2026.09.16.26363254v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.06.003"},{"key":"2026092504251615000_2026.09.16.26363254v1.52","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055695"},{"key":"2026092504251615000_2026.09.16.26363254v1.53","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1002\/ajmg.a.37892","article-title":"Two cases with de novo 3q26.31 microdeletion suggest a role for FNDC3B in human craniofacial development","volume":"170","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"2026092504251615000_2026.09.16.26363254v1.54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.452961"},{"key":"2026092504251615000_2026.09.16.26363254v1.55","first-page":"352","article-title":"Novel VCAN mutations and evidence for unbalanced alternative splicing in the pathogenesis of Wagner syndrome","volume":"21","year":"2012","journal-title":"Eur. J. Hum. Genet"},{"key":"2026092504251615000_2026.09.16.26363254v1.56","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bbrc.2022.12.086","article-title":"Single-cell transcriptome analysis identifies Versican(+) myofibroblast as a hallmark for thoracic aortic aneurysm marked by activation of PI3K-AKT signaling pathway","volume":"643","year":"2023","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2026092504251615000_2026.09.16.26363254v1.57","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.122.318135"},{"key":"2026092504251615000_2026.09.16.26363254v1.58","doi-asserted-by":"crossref","first-page":"101353","DOI":"10.1016\/j.jacbts.2025.101353","article-title":"Focal adhesion kinase drives Rho\/ROCK and mTOR signaling to protect and augment aortic dissections","volume":"10","year":"2025","journal-title":"JACC Basic Transl. Sci"},{"key":"2026092504251615000_2026.09.16.26363254v1.59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002293"},{"key":"2026092504251615000_2026.09.16.26363254v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2010.59"},{"key":"2026092504251615000_2026.09.16.26363254v1.61","doi-asserted-by":"crossref","first-page":"5966","DOI":"10.1038\/ncomms6966","article-title":"Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci","volume":"6","year":"2015","journal-title":"Nat. Commun"},{"key":"2026092504251615000_2026.09.16.26363254v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.011"},{"key":"2026092504251615000_2026.09.16.26363254v1.63","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/15548627.2022.2080383","article-title":"An intrinsically disordered protein region encoded by the human disease gene CLEC16A regulates mitophagy","volume":"19","year":"2023","journal-title":"Autophagy"},{"key":"2026092504251615000_2026.09.16.26363254v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2025.09.009"},{"key":"2026092504251615000_2026.09.16.26363254v1.65","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.051171"},{"key":"2026092504251615000_2026.09.16.26363254v1.66","doi-asserted-by":"crossref","first-page":"bpaf031","DOI":"10.1093\/biomethods\/bpaf031","article-title":"Measurement of oxygen consumption rate in mouse aortic tissue","volume":"10","year":"2025","journal-title":"Biol. Methods Protoc"},{"key":"2026092504251615000_2026.09.16.26363254v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.020"},{"key":"2026092504251615000_2026.09.16.26363254v1.68","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01327.x"},{"key":"2026092504251615000_2026.09.16.26363254v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06922-7"},{"key":"2026092504251615000_2026.09.16.26363254v1.70","first-page":"42","article-title":"Critical role of cytosolic DNA and its sensing adaptor STING in aortic degeneration, dissection, and rupture","volume":"141","year":"2019","journal-title":"Circulation"},{"key":"2026092504251615000_2026.09.16.26363254v1.71","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1111"},{"key":"2026092504251615000_2026.09.16.26363254v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.02.001"},{"key":"2026092504251615000_2026.09.16.26363254v1.73","first-page":"2165","article-title":"Transcription factor cAMP response element modulator (Crem) restrains Pdgf-dependent proliferation of vascular smooth muscle cells in mice","volume":"467","year":"2014","journal-title":"Pflugers Arch"},{"key":"2026092504251615000_2026.09.16.26363254v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2024.103733"},{"key":"2026092504251615000_2026.09.16.26363254v1.75","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-2694"},{"key":"2026092504251615000_2026.09.16.26363254v1.76","doi-asserted-by":"publisher","DOI":"10.7150\/thno.42869"},{"key":"2026092504251615000_2026.09.16.26363254v1.77","doi-asserted-by":"crossref","first-page":"115280","DOI":"10.1016\/j.bcp.2022.115280","article-title":"Short-term rapamycin treatment increases life span and attenuates aortic aneurysm in a murine model of Marfan-Syndrome","volume":"205","year":"2022","journal-title":"Biochem. Pharmacol"},{"key":"2026092504251615000_2026.09.16.26363254v1.78","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310563"},{"key":"2026092504251615000_2026.09.16.26363254v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11389-1"},{"key":"2026092504251615000_2026.09.16.26363254v1.80","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jacbts.2023.07.014","article-title":"The antioxidant\/nitric oxide-quenching agent cobinamide prevents aortic disease in a mouse model of Marfan Syndrome","volume":"9","year":"2024","journal-title":"JACC Basic Transl. Sci"},{"key":"2026092504251615000_2026.09.16.26363254v1.81","doi-asserted-by":"crossref","first-page":"100243","DOI":"10.1016\/j.jvssci.2024.100243","article-title":"Genome-first approach to rare and common variant risk of thoracic aortic aneurysm and dissection","volume":"5","year":"2024","journal-title":"JVS Vasc. Sci"},{"key":"2026092504251615000_2026.09.16.26363254v1.82","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1078"},{"key":"2026092504251615000_2026.09.16.26363254v1.83","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04558-8"},{"key":"2026092504251615000_2026.09.16.26363254v1.84","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"2026092504251615000_2026.09.16.26363254v1.85","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","year":"2012","journal-title":"Fly (Austin)"},{"key":"2026092504251615000_2026.09.16.26363254v1.86","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2012.00035"},{"key":"2026092504251615000_2026.09.16.26363254v1.87","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00803-9"},{"key":"2026092504251615000_2026.09.16.26363254v1.88","doi-asserted-by":"crossref","unstructured":"Stromberg M , Roy R , Lajugie J , Jiang Y , Li H , Margulies E. Nirvana . In: Proceedings of the 8th ACM International Conference on Bioinformatics, Computational Biology,and Health Informatics. New York, NY, USA: ACM; 2017. p. 596\u2013596.","DOI":"10.1145\/3107411.3108204"},{"key":"2026092504251615000_2026.09.16.26363254v1.89","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"2026092504251615000_2026.09.16.26363254v1.90","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01943-7"},{"key":"2026092504251615000_2026.09.16.26363254v1.91","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"DoubletFinder: Doublet detection in single-cell RNA sequencing data using artificial nearest neighbors","volume":"8","year":"2019","journal-title":"Cell Syst"},{"key":"2026092504251615000_2026.09.16.26363254v1.92","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz698"},{"key":"2026092504251615000_2026.09.16.26363254v1.93","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.73600.2"},{"key":"2026092504251615000_2026.09.16.26363254v1.94","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-023-01767-Y"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.16.26363254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:25:28Z","timestamp":1790335528000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.09.16.26363254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":94,"URL":"https:\/\/doi.org\/10.64898\/2026.09.16.26363254","relation":{},"subject":[],"published":{"date-parts":[[2026,9,22]]},"subtype":"preprint"}}