Journal
NATURE GENETICS
Volume 51, Issue 11, Pages 1580-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41588-019-0514-8
Keywords
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Categories
Funding
- NHLBI [N01-HC-25195, R01HL142809, K08HL111210, N02-HL-64278, RO1-HL-67348]
- Affymetrix for genotyping services [N02-HL-6-4278]
- American Heart Association [18TPA34230025, 15FTF25980003]
- Wild Family Foundation
- Hassenfeld Scholar Award
- Deutsche Forschungsgemeinschaft (DFG) [Wu 841/1-1]
- Department of Defense [W81XWH-17-1-0058]
- Swedish research council [2016-00598]
- Fredman Fellowship
- Toomey Fund for Aortic Dissection Research
- Leducq Foundation
- National Institutes of Diabetes and Digestive and Kidney Diseases [5R01DK082971]
- National Institute on Aging (NIA) [N01-AG-12100]
- National Eye Institute
- National Institute on Deafness and Other Communication Disorders
- NHLBI
- NIA Intramural Research Program
- Hjartavernd (the Icelandic Heart Association)
- Althingi (Icelandic Parliament)
- National Center for Advancing Translational Sciences
- Clinical Translational Science Institute [UL1TR001881]
- National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) Diabetes Research Center (DRC) [DK063491]
- NIH [R01HL071739, MD012765, DK117445, HL140385]
- NIH from the NHLBI [R01-HL-117078]
- NIDDK [R01-DK-089256, R01-DK-071891]
- Heinz Nixdorf Foundation
- German Ministry of Education and Science
- DFG [ER 155/6-1, ER 155/6-2, PE 2309/2-1]
- Imatron
- Sarstedt AG Co.
- Ministry of Culture and Science of North Rhine-Westphalia
- Faculty of Medicine, University Duisburg-Essen
- DFG (German Research Foundation) through the Transregional Collaborative Research Centre [TRR259, 426128588]
- DFG under Germany's Excellence Strategy-EXC2151 [390873048]
- General Clinical Research Center of Wake Forest School of Medicine [M01-RR-07122]
- GE-Imatron
- [R01 HL130113]
- [R01 HL071739]
- [R01 HL72403]
- [HHSN268201500003I]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-000040]
- [UL1-TR-001079]
- [UL1-TR-001420]
- Swedish Research Council [2016-00598] Funding Source: Swedish Research Council
Ask authors/readers for more resources
Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 x 10(-8)). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.
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