Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci
| العنوان: | Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci |
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| المؤلفون: | Thomas Quertermous, Jonathan D. Lee, Stephen B. Montgomery, Ulf Hedin, Arno Ruusalepp, Deshna Majmudar, Juyong Brian Kim, Ramendra K. Kundu, Ting Wang, Milos Pjanic, Christer Betsholtz, Oliver Wang, Ariella Cohain, Johan Björkegren, Themistocles L. Assimes, Eric E. Schadt, Oscar Franzén, Ljubica Perisic, Trieu Nguyen, Clint L. Miller |
| المصدر: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-16 (2016) |
| بيانات النشر: | Nature Publishing Group, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Science, Myocytes, Smooth Muscle, Primary Cell Culture, Quantitative Trait Loci, General Physics and Astronomy, Coronary Artery Disease, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, Coronary artery disease, 03 medical and health sciences, Environmental risk, Basic Helix-Loop-Helix Transcription Factors, Medicine, Humans, Cardiac and Cardiovascular Systems, Genetic Predisposition to Disease, Alleles, Genetic association, Multidisciplinary, Kardiologi, Base Sequence, business.industry, Genome, Human, Gene Expression Profiling, General Chemistry, Genomics, medicine.disease, Coronary Vessels, Chromatin, 3. Good health, Transcription Factor AP-1, 030104 developmental biology, Gene Expression Regulation, business, Functional genomics, Genome-Wide Association Study |
| الوصف: | Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps, we prioritize 64 candidate variants and perform allele-specific binding and expression analyses at seven top candidate loci: 9p21.3, SMAD3, PDGFD, IL6R, BMP1, CCDC97/TGFB1 and LMOD1. We validate our findings in expression quantitative trait loci cohorts, which together reveal new links between CAD associations and regulatory function in the appropriate disease context. Coronary heart disease is the leading cause of death worldwide with multiple environmental and genetic risk factors. Here the authors integrate genomic, epigenomic and transcriptomic mapping to elucidate causal variation and mechanisms of known genetic associations. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::04f3d636fdc5d7ffc8d8944fbccabdbfTest http://europepmc.org/articles/PMC4941121Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....04f3d636fdc5d7ffc8d8944fbccabdbf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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