Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target
Department of Internal Medicine, Division of Cardiology, University of Michigan, MI, Ann Arbor, United States; Department of Genetics, Yale School of Medicine, CT, New Haven, United States.
Department of Surgery, Stanford University School of Medicine, CA, Stanford, United States; VA Palo Alto Healthcare System, CA, Palo Alto, United States.
Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, PA, Philadelphia, United States.
VA Palo Alto Healthcare System, CA, Palo Alto, United States; Department of Medicine, Stanford University School of Medicine, CA, Stanford, United States; Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, Stanford, United States.
Show others and affiliations
2023 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 55, no 11, p. 1831-1842Article in journal (Refereed) Published
Abstract [en]

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 55, no 11, p. 1831-1842
National Category
Medical Genetics and Genomics Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:umu:diva-215841DOI: 10.1038/s41588-023-01510-yISI: 001085082700001PubMedID: 37845353Scopus ID: 2-s2.0-85174309497OAI: oai:DiVA.org:umu-215841DiVA, id: diva2:1809826
Funder
Novo Nordisk Foundation, NNF17OC0027594Novo Nordisk Foundation, NNF14CC0001Novo Nordisk Foundation, NNF20OC0065799EU, Horizon 2020, 848146Available from: 2023-11-06 Created: 2023-11-06 Last updated: 2025-04-24Bibliographically approved

Open Access in DiVA

fulltext(4048 kB)58 downloads
File information
File name FULLTEXT02.pdfFile size 4048 kBChecksum SHA-512
9ff454e7436c626748469e5caa75f28025f3c0c54e53ef63fad245e9e05e4723a63a227e562576a0ab665803e62a9363e8f2e5e91bba2c95ceaf563ed8b40ffb
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Wanhainen, Anders

Search in DiVA

By author/editor
Wanhainen, Anders
By organisation
Surgery
In the same journal
Nature Genetics
Medical Genetics and GenomicsCardiology and Cardiovascular Disease

Search outside of DiVA

GoogleGoogle Scholar
Total: 78 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 285 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf