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FältnamnIndikatorerMetadata
00008798naa a2200925 4500
001oai:DiVA.org:umu-170494
003SwePub
008200507s2020 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:2dfa9178-9252-42bb-9b80-f98b68c8b76a
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1704942 URI
0247 a https://doi.org/10.1001/jamacardio.2020.02462 DOI
0247 a https://lup.lub.lu.se/record/2dfa9178-9252-42bb-9b80-f98b68c8b76a2 URI
040 a (SwePub)umud (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Chen, Hao Yuu McGill University Health Center,McGill University4 aut
2451 0a Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
264 1b American Medical Association (AMA),c 2020
338 a electronic2 rdacarrier
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653 a medicin
653 a Medicine
7001 a Cairns, Benjamin J.u University of Oxford4 aut
7001 a Small, Aeron M.u Cochin Hospital4 aut
7001 a Burr, Hannah A.u McGill University Health Center,McGill University4 aut
7001 a Ambikkumar, Athithanu University of California, Davis4 aut
7001 a Martinsson, Andreasu 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 Hospital4 aut0 (Swepub:lu)med-asm
7001 a Thériault, Sébastienu Institut universitaire de cardiologie et de pneumologie de Québec4 aut
7001 a Munter, Hans Markusu McGill University4 aut
7001 a Steffen, Brianu University of Minnesota4 aut
7001 a Zhang, Richardu McGill University Health Center4 aut
7001 a Levinson, Rebecca T.u Vanderbilt University4 aut
7001 a Shaffer, Christian M.u Vanderbilt University4 aut
7001 a Rong, Jianu Boston University,National Heart Lung and Blood Institute4 aut
7001 a Sonestedt, Emilyu Lund University,Lunds universitet,Nutritionsepidemiologi,Forskargrupper vid Lunds universitet,Nutrition Epidemiology,Lund University Research Groups4 aut0 (Swepub:lu)medf-eso
7001 a Dufresne, Lineu McGill University Health Center4 aut
7001 a Ljungberg, Johanu Umeå University,Umeå universitet,Kardiologi4 aut0 (Swepub:umu)jonljg02
7001 a Näslund, Ulfu Umeå University,Umeå universitet,Kardiologi4 aut0 (Swepub:umu)ulna0002
7001 a Johansson, Bengtu Umeå University,Umeå universitet,Kardiologi,Institut universitaire de cardiologie et de pneumologie de Québec4 aut0 (Swepub:umu)bejo0003
7001 a Ranatunga, Dilrini K.u Kaiser Permanente4 aut
7001 a Whitmer, Rachel A.4 aut
7001 a Budoff, Matthew J.u University of California, Los Angeles4 aut
7001 a Nguyen, Albertu McGill University Health Center4 aut
7001 a Vasan, Ramachandran S.u Umeå University4 aut
7001 a Larson, Martin G.u National Heart Lung and Blood Institute,Boston University4 aut
7001 a Harris, William S.4 aut
7001 a Damrauer, Scott M.u Cochin Hospital4 aut
7001 a Stark, Ken D.u University of Waterloo4 aut
7001 a Boekholdt, S. Matthijsu Academic Medical Center of University of Amsterdam (AMC)4 aut
7001 a Wareham, Nicholas J.u University of Cambridge4 aut
7001 a Pibarot, Philippeu Institut universitaire de cardiologie et de pneumologie de Québec4 aut
7001 a Arsenault, Benoit J.4 aut
7001 a Mathieu, Patricku Institut universitaire de cardiologie et de pneumologie de Québec4 aut
7001 a Gudnason, Vilmunduru University of Iceland4 aut
7001 a O'Donnell, Christopher J.u National Heart Lung and Blood Institute,Boston University4 aut
7001 a Rotter, Jerome I.u University of California, Los Angeles4 aut
7001 a Tsai, Michael Y.u University of Minnesota4 aut
7001 a Post, Wendy S.u Johns Hopkins University4 aut
7001 a Clarke, Robertu University of Oxford4 aut
7001 a Söderberg, Stefanu Umeå universitet,Kardiologi,Vanderbilt University4 aut0 (Swepub:umu)stso0001
7001 a Bossé, Yohanu Institut universitaire de cardiologie et de pneumologie de Québec4 aut
7001 a Wells, Quinn S.4 aut
7001 a Smith, J. Gustavu 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 Hospital4 aut0 (Swepub:lu)med-gvs
7001 a Rader, Daniel J.u Cochin Hospital4 aut
7001 a Lathrop, Marku McGill University4 aut
7001 a Engert, James C.u McGill University Health Center,McGill University4 aut
7001 a Thanassoulis, Georgeu McGill University,McGill University Health Center4 aut
7102 a McGill University Health Centerb McGill University4 org
7730 t JAMA cardiologyd : American Medical Association (AMA)g 5:6, s. 694-702q 5:6<694-702x 2380-6583x 2380-6591
8564 u https://doi.org/10.1001/jamacardio.2020.0246y Fulltext
8564 u https://umu.diva-portal.org/smash/get/diva2:1428924/FULLTEXT02.pdfx primaryx Raw objecty fulltext:print
8564 u https://jamanetwork.com/journals/jamacardiology/articlepdf/2762845/jamacardiology_chen_2020_oi_200009.pdf
8564 u http://dx.doi.org/10.1001/jamacardio.2020.0246x freey FULLTEXT
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170494
8564 8u https://doi.org/10.1001/jamacardio.2020.0246
8564 8u https://lup.lub.lu.se/record/2dfa9178-9252-42bb-9b80-f98b68c8b76a

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