Deep learning enables genetic analysis of the human thoracic aorta.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
11
05
2020
accepted:
30
09
2021
pubmed:
28
11
2021
medline:
24
2
2022
entrez:
27
11
2021
Statut:
ppublish
Résumé
Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (hazard ratio = 1.43 per s.d., confidence interval 1.32-1.54, P = 3.3 × 10
Identifiants
pubmed: 34837083
doi: 10.1038/s41588-021-00962-4
pii: 10.1038/s41588-021-00962-4
pmc: PMC8758523
mid: NIHMS1745044
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-51Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL159346
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL139731
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141434
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL092577
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL140187
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007208
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL105780
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL140224
Pays : United States
Organisme : NHLBI NIH HHS
ID : U54 HL120163
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128914
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 18SFRN34250007
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL153669
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL134893
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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