{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:38:22Z","timestamp":1792647502578,"version":"4.5.0"},"reference-count":82,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Aortic dissection (AD) is a lethal cardiovascular emergency with a complex and underexplored genetic basis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We performed whole\u2010genome sequencing on 151 patients with sporadic Stanford type B AD and 965 healthy controls in a Chinese population as a discovery phase analysis to assess both common and rare variants. Cross\u2010ancestry meta\u2010analyses incorporating 4 external genome\u2010wide association data sets were used to identify population\u2010specific risk loci. To pinpoint functional candidates, we integrated epigenomic profiles and single\u2010cell transcriptomes from human aortic tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Whole\u2010genome sequencing analysis identified 21 candidate common loci and 2 low\u2010frequency variants associated with AD in this discovery cohort. Two candidate common variants in the human leukocyte antigen region (rs9260945 near\n                      <jats:italic toggle=\"no\">HLA\u2010A<\/jats:italic>\n                      and rs9276409 within\n                      <jats:italic toggle=\"no\">HLA\u2010DQA2<\/jats:italic>\n                      ) showed strong associations and colocalized with regulatory elements in aortic and immune cells, indicating immune\u2010mediated vascular pathology. A low\u2010frequency missense variant in the\n                      <jats:italic toggle=\"no\">COG5<\/jats:italic>\n                      gene (rs1203229795, effect allele frequency=0.019) emerged as an independent AD risk factor, likely affecting extracellular matrix glycosylation. Single\u2010cell transcriptomic analysis of AD\u2010associated variants in human aortic tissues demonstrated enhanced interactions among fibroblasts, vascular smooth muscle cells, and macrophages, supporting their roles in AD pathogenesis. Integrated gene\u2010based and expression analyses further highlighted\n                      <jats:italic toggle=\"no\">TPM4<\/jats:italic>\n                      , a marker of vascular smooth muscle cell dedifferentiation, as a putative susceptibility gene in AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This multiomics investigation expands the genetic landscape of sporadic AD in Chinese individuals, revealing immune\u2010related human leukocyte antigen loci and a functionally supported candidate\n                      <jats:italic toggle=\"no\">COG5<\/jats:italic>\n                      variant. Our findings offer new insights into AD pathogenesis and identify candidate targets for future diagnostic and therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.126.050327","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:57:35Z","timestamp":1791633455000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Whole\u2010Genome Sequencing and Single\u2010Cell Transcriptomics Identify Human Leukocyte Antigen Loci and a\n                    <i>COG5<\/i>\n                    Variant in Aortic Dissection"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-071X","authenticated-orcid":false,"given":"Jinran","family":"Lin","sequence":"first","affiliation":[{"name":"Human Phenome Institute, Fudan University","place":["Shanghai, China"]},{"name":"Fudan University","place":["Shanghai, 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