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Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity

التفاصيل البيبلوغرافية
العنوان: Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity
المؤلفون: Harper, A. R., Goel, A., Grace, C., Thomson, K. L., Petersen, S. E., Xu, X., Waring, A., Ormondroyd, E., Kramer, C. M., C. Y., Ho, Neubauer, S., Kolm, P., Kwong, R., Dolman, S. F., Desvigne-Nickens, P., Dimarco, J. P., Geller, N., Kim, D. -Y., Zhang, C., Weintraub, W., Abraham, T., Anderson, L., Appelbaum, E., Autore, C., Berry, C., Biagini, E., Bradlow, W., Bucciarelli-Ducci, C., Chiribiri, A., Choudhury, L., Crean, A., Dawson, D., Desai, M. Y., Elstein, E., Flett, A., Friedrich, M., Heitner, S., Helms, A., Jacoby, D. L., Kim, H., Kim, B., Larose, E., Mahmod, M., Mahrholdt, H., Maron, M., Mccann, G., Michels, M., Mohiddin, S., Nagueh, S., Newby, D., Olivotto, I., Owens, A., Pierre-Mongeon, F., Prasad, S., Rimoldi, O., Salerno, M., Schulz-Menger, J., Sherrid, M., Swoboda, P., van Rossum, A., Weinsaft, J., White, J., Williamson, E., Tadros, R., Ware, J. S., Bezzina, C. R., Farrall, M., Watkins, H.
المساهمون: Cardiology, ACS - Heart failure & arrhythmias
المصدر: Nature genetics, 53(2), 135-142. Nature Publishing Group
بيانات النشر: Nature Research, 2021.
سنة النشر: 2021
مصطلحات موضوعية: LOCI, Genome-wide association study, Blood Pressure, Bioinformatics, DISEASE, SYSTOLIC HYPERTENSION, 0302 clinical medicine, Adolescent, Adult, Aged, Cardiac Myosins, Cardiomyopathy, Hypertrophic, Carrier Proteins, Case-Control Studies, Formins, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Humans, Middle Aged, Myosin Heavy Chains, Risk Factors, Sarcomeres, Young Adult, Polymorphism, Single Nucleotide, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Hypertrophic cardiomyopathy, Single Nucleotide, 3. Good health, GENOTYPE, cardiovascular system, Life Sciences & Biomedicine, Cardiomyopathy, macromolecular substances, Biology, AMERICAN-COLLEGE, 03 medical and health sciences, Heart disorder, Mendelian randomization, Genetics, medicine, Expressivity (genetics), cardiovascular diseases, Risk factor, GENOME-WIDE ASSOCIATION, Polymorphism, 030304 developmental biology, HCMR Investigators, Science & Technology, Genetic heterogeneity, Case-control study, 06 Biological Sciences, medicine.disease, Hypertrophic, DISCOVERY, 030217 neurology & neurosurgery, Developmental Biology
الوصف: Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h2g = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.
وصف الملف: application/pdf
اللغة: English
تدمد: 1546-1718
1061-4036
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9e728b626e4b4ceef5caa71d49ae9b7
http://hdl.handle.net/11573/1576508
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....e9e728b626e4b4ceef5caa71d49ae9b7
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15461718
10614036