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Association of FADS...
Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
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- Chen, Hao Yu (författare)
- McGill University Health Center,McGill University
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- Cairns, Benjamin J. (författare)
- University of Oxford
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- Small, Aeron M. (författare)
- Cochin Hospital
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visa fler...
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- Burr, Hannah A. (författare)
- McGill University Health Center,McGill University
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- Ambikkumar, Athithan (författare)
- University of California, Davis
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- Martinsson, Andreas (författare)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Skåne University Hospital
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- Thériault, Sébastien (författare)
- Institut universitaire de cardiologie et de pneumologie de Québec
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- Munter, Hans Markus (författare)
- McGill University
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- Steffen, Brian (författare)
- University of Minnesota
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- Zhang, Richard (författare)
- McGill University Health Center
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- Levinson, Rebecca T. (författare)
- Vanderbilt University
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- Shaffer, Christian M. (författare)
- Vanderbilt University
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- Rong, Jian (författare)
- Boston University,National Heart Lung and Blood Institute
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- Sonestedt, Emily (författare)
- Lund University,Lunds universitet,Nutritionsepidemiologi,Forskargrupper vid Lunds universitet,Nutrition Epidemiology,Lund University Research Groups
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- Dufresne, Line (författare)
- McGill University Health Center
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- Ljungberg, Johan (författare)
- Umeå University,Umeå universitet,Kardiologi
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- Näslund, Ulf (författare)
- Umeå University,Umeå universitet,Kardiologi
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- Johansson, Bengt (författare)
- Umeå University,Umeå universitet,Kardiologi,Institut universitaire de cardiologie et de pneumologie de Québec
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- Ranatunga, Dilrini K. (författare)
- Kaiser Permanente
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Whitmer, Rachel A. (författare)
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- Budoff, Matthew J. (författare)
- University of California, Los Angeles
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- Nguyen, Albert (författare)
- McGill University Health Center
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- Vasan, Ramachandran S. (författare)
- Umeå University
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- Larson, Martin G. (författare)
- National Heart Lung and Blood Institute,Boston University
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Harris, William S. (författare)
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- Damrauer, Scott M. (författare)
- Cochin Hospital
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- Stark, Ken D. (författare)
- University of Waterloo
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- Boekholdt, S. Matthijs (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Wareham, Nicholas J. (författare)
- University of Cambridge
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- Pibarot, Philippe (författare)
- Institut universitaire de cardiologie et de pneumologie de Québec
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Arsenault, Benoit J. (författare)
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- Mathieu, Patrick (författare)
- Institut universitaire de cardiologie et de pneumologie de Québec
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- Gudnason, Vilmundur (författare)
- University of Iceland
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- O'Donnell, Christopher J. (författare)
- National Heart Lung and Blood Institute,Boston University
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- Rotter, Jerome I. (författare)
- University of California, Los Angeles
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- Tsai, Michael Y. (författare)
- University of Minnesota
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- Post, Wendy S. (författare)
- Johns Hopkins University
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- Clarke, Robert (författare)
- University of Oxford
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- Söderberg, Stefan (författare)
- Umeå universitet,Kardiologi,Vanderbilt University
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- Bossé, Yohan (författare)
- Institut universitaire de cardiologie et de pneumologie de Québec
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Wells, Quinn S. (författare)
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- Smith, J. Gustav (författare)
- Lund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital
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- Rader, Daniel J. (författare)
- Cochin Hospital
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- Lathrop, Mark (författare)
- McGill University
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- Engert, James C. (författare)
- McGill University Health Center,McGill University
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- Thanassoulis, George (författare)
- McGill University,McGill University Health Center
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(creator_code:org_t)
- American Medical Association (AMA), 2020
- 2020
- Engelska.
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://jamanetwork....
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
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- medicin
- Medicine
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Chen, Hao Yu
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Cairns, Benjamin ...
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Small, Aeron M.
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Burr, Hannah A.
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Ambikkumar, Athi ...
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Martinsson, Andr ...
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visa fler...
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Thériault, Sébas ...
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Munter, Hans Mar ...
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Steffen, Brian
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Zhang, Richard
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Levinson, Rebecc ...
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Shaffer, Christi ...
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Rong, Jian
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Sonestedt, Emily
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Dufresne, Line
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Ljungberg, Johan
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Näslund, Ulf
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Johansson, Bengt
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Ranatunga, Dilri ...
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Whitmer, Rachel ...
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Budoff, Matthew ...
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Nguyen, Albert
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Vasan, Ramachand ...
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Larson, Martin G ...
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Harris, William ...
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Damrauer, Scott ...
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Stark, Ken D.
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Boekholdt, S. Ma ...
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Wareham, Nichola ...
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Pibarot, Philipp ...
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Arsenault, Benoi ...
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Mathieu, Patrick
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Gudnason, Vilmun ...
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O'Donnell, Chris ...
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Rotter, Jerome I ...
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Tsai, Michael Y.
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Post, Wendy S.
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Clarke, Robert
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Söderberg, Stefa ...
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Bossé, Yohan
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Wells, Quinn S.
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Smith, J. Gustav
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Rader, Daniel J.
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Lathrop, Mark
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Engert, James C.
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Thanassoulis, Ge ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
- Artiklar i publikationen
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JAMA cardiology
- Av lärosätet
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Umeå universitet
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Lunds universitet