دورية أكاديمية
Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.
| العنوان: | Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect. |
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| المؤلفون: | Tadros R; Cardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada. rafik.tadros@umontreal.ca.; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. rafik.tadros@umontreal.ca., Francis C; Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.; National Heart and Lung Institute, Imperial College London, London, UK., Xu X; MRC London Institute of Medical Sciences, Imperial College London, London, UK., Vermeer AMC; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Clinical Genetics, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-HEART)., Harper AR; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; Wellcome Centre for Human Genetics, Oxford, UK., Huurman R; Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands., Kelu Bisabu K; Cardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada., Walsh R; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Hoorntje ET; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; Netherlands Heart Institute, Utrecht, the Netherlands., Te Rijdt WP; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.; Netherlands Heart Institute, Utrecht, the Netherlands., Buchan RJ; Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.; National Heart and Lung Institute, Imperial College London, London, UK., van Velzen HG; Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands., van Slegtenhorst MA; Department of Clinical Genetics, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands., Vermeulen JM; Department of Psychiatry, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Offerhaus JA; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Bai W; Data Science Institute, Imperial College London, London, UK.; Department of Brain Sciences and UK Dementia Research Institute at Imperial College London, Hammersmith Hospital, Imperial College London, London, UK., de Marvao A; MRC London Institute of Medical Sciences, Imperial College London, London, UK., Lahrouchi N; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Beekman L; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Karper JC; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Veldink JH; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Kayvanpour E; Institute for Cardiomyopathies, Heidelberg Heart Center, University of Heidelberg, Heidelberg, Germany.; DZHK (German Center for Cardiovascular Research), Berlin, Germany., Pantazis A; Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK., Baksi AJ; Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.; National Heart and Lung Institute, Imperial College London, London, UK., Whiffin N; Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.; 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The Francis Crick Institute, London, UK.; Department of Epidemiology and Biostatistics, Imperial College London, London, UK., Elliott P; Department of Epidemiology and Biostatistics, Imperial College London, London, UK., Richard P; Service de biochimie métabolique, UF de cardiogénétique et myogénétique moléculaire et cellulaire, APHP, Hôpital Pitié-Salpêtrière, Paris, France.; INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Faculté de Médecine, Sorbonne Université, Paris, France., Ader F; Service de biochimie métabolique, UF de cardiogénétique et myogénétique moléculaire et cellulaire, APHP, Hôpital Pitié-Salpêtrière, Paris, France.; INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Faculté de Médecine, Sorbonne Université, Paris, France.; Faculté de Pharmacie, Université de Paris, Paris, France., Villard E; INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Faculté de Médecine, Sorbonne Université, Paris, France., Lichtner P; 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National Heart and Lung Institute, Imperial College London, London, UK., Cook SA; National Heart and Lung Institute, Imperial College London, London, UK.; MRC London Institute of Medical Sciences, Imperial College London, London, UK.; National Heart Research Institute Singapore, National Heart Center Singapore, Singapore, Singapore.; Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Prasad SK; Cardiovascular Research Centre, Royal Brompton and Harefield National Health Service Foundation Trust, London, UK.; National Heart and Lung Institute, Imperial College London, London, UK., O'Regan DP; MRC London Institute of Medical Sciences, Imperial College London, London, UK., van der Velden J; Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Amsterdam, the Netherlands., Verweij KJH; Department of Psychiatry, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Talajic M; Cardiovascular Genetics Center, Montreal Heart Institute, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada., Lettre G; 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MRC London Institute of Medical Sciences, Imperial College London, London, UK. j.ware@imperial.ac.uk., Bezzina CR; Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. c.r.bezzina@amsterdamumc.nl.; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-HEART), . c.r.bezzina@amsterdamumc.nl. |
| المصدر: | Nature genetics [Nat Genet] 2021 Feb; Vol. 53 (2), pp. 128-134. Date of Electronic Publication: 2021 Jan 25. |
| نوع المنشور: | Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Co., c1992- |
| مواضيع طبية MeSH: | Cardiomyopathy, Dilated/*genetics , Cardiomyopathy, Hypertrophic/*genetics, Cardiomyopathy, Dilated/mortality ; Cardiomyopathy, Dilated/physiopathology ; Cardiomyopathy, Hypertrophic/mortality ; Cardiomyopathy, Hypertrophic/physiopathology ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Heart Ventricles/physiopathology ; Humans ; Kaplan-Meier Estimate ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Ventricular Function, Left/genetics |
| مستخلص: | The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects. |
| التعليقات: | Comment in: Nat Rev Cardiol. 2021 Apr;18(4):229. (PMID: 33564142) |
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| معلومات مُعتمدة: | MR/K501013/1 United Kingdom MRC_ Medical Research Council; 107469 United Kingdom WT_ Wellcome Trust; MC_UP_1605/13 United Kingdom MRC_ Medical Research Council; MR/N026934/1 United Kingdom MRC_ Medical Research Council; G0300665 United Kingdom MRC_ Medical Research Council; MC_PC_17114 United Kingdom MRC_ Medical Research Council; 107469/Z/15/Z United Kingdom WT_ Wellcome Trust; RG/19/6/34387 United Kingdom BHF_ British Heart Foundation; ZONMW_91815610 Netherlands ZONMW_ ZonMw; G9409531 United Kingdom MRC_ Medical Research Council; G0900897 United Kingdom MRC_ Medical Research Council; FS/15/81/31817 United Kingdom BHF_ British Heart Foundation; MC_UP_1102/19 United Kingdom MRC_ Medical Research Council; United Kingdom DH_ Department of Health; 087183 United Kingdom WT_ Wellcome Trust; MR/S003754/1 United Kingdom MRC_ Medical Research Council; MC_UP_1102/20 United Kingdom MRC_ Medical Research Council; U01 HL117006 United States HL NHLBI NIH HHS; G9901399 United Kingdom MRC_ Medical Research Council; MC_U120085815 United Kingdom MRC_ Medical Research Council; G0601966 United Kingdom MRC_ Medical Research Council; RE/13/1/30181 United Kingdom BHF_ British Heart Foundation; 090532/Z/09/Z United Kingdom WT_ Wellcome Trust; RG/18/9/33887 United Kingdom BHF_ British Heart Foundation; RE/18/4/34215 United Kingdom BHF_ British Heart Foundation; United Kingdom WT_ Wellcome Trust; G9409634 United Kingdom MRC_ Medical Research Council; G0100811 United Kingdom MRC_ Medical Research Council; SP/17/11/32885 United Kingdom BHF_ British Heart Foundation; MR/M024903/1 United Kingdom MRC_ Medical Research Council; NH/17/1/32725 United Kingdom BHF_ British Heart Foundation |
| تواريخ الأحداث: | Date Created: 20210126 Date Completed: 20210304 Latest Revision: 20240212 |
| رمز التحديث: | 20240212 |
| مُعرف محوري في PubMed: | PMC7611259 |
| DOI: | 10.1038/s41588-020-00762-2 |
| PMID: | 33495596 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1546-1718 |
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| DOI: | 10.1038/s41588-020-00762-2 |