title: Dissecting the roles of microRNAs in coronary heart disease via integrative genomic analyses.
abstract: OBJECTIVE
  The roles of microRNAs (miRNAs) in coronary heart disease (CHD) have not been well characterized. This study sought to systematically characterize the complex genomic architecture of CHD by integrating whole blood miRNA and mRNA expression with genetic variation in 186 CHD cases and 186 controls.
  
  
  RESULTS
  At false discovery rate <0.2, 15 miRNAs were differentially expressed between CHD cases and controls. To explore regulatory mechanisms, we integrated miRNA and mRNA expression with genome-wide genotype data to investigate miRNA and mRNA associations and relationships of genetic variation with miRNAs. We identified a large number of correlated miRNA-mRNA pairs and genetic loci that seem to regulate miRNA levels. Subsequently, we explored the relationships of these complex molecular associations with CHD status. We identified a large difference in miRNA-mRNA associations between CHD cases and controls, as demonstrated by a significantly higher proportion of inversely correlated miRNA-mRNA pairs in cases versus controls (80% versus 30%; P<1×10(-16)), suggesting a genome-wide shift in the regulatory structure of the transcriptome in CHD. The differentially coexpressed miRNA-mRNA pairs showed enrichment for CHD risk genetic variants affecting both miRNA and mRNA expression levels, implicating a putatively causal role in CHD. Furthermore, 3 miRNAs (miR-1275, miR-365a-3p, and miR-150-5p) were associated with an mRNA coexpression module that was causally linked to CHD and reflected the dysregulation of B-cell centered immune function.
  
  
  CONCLUSIONS
  Our results provide novel evidence that miRNAs are important regulators of biological processes involved in CHD via genetic control and via their tight coexpression with mRNAs.
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Tianxiao
authors: T
authors: Huan
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Jian
authors: J
authors: Rong
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Kahraman
authors: K
authors: Tanriverdi
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Qingying
authors: Q
authors: Meng
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Anindya
authors: A
authors: Bhattacharya
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: David D
authors: DD
authors: McManus
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Roby
authors: R
authors: Joehanes
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Themistocles L
authors: TL
authors: Assimes
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Ruth
authors: R
authors: McPherson
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Nilesh J
authors: NJ
authors: Samani
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Jeanette
authors: J
authors: Erdmann
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Heribert
authors: H
authors: Schunkert
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Paul
authors: P
authors: Courchesne
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Peter J
authors: PJ
authors: Munson
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Andrew D
authors: AD
authors: Johnson
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Bin
authors: B
authors: Zhang
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Martin G
authors: MG
authors: Larson
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.). jane.freedman@umassmed.edu Levyd@nih.gov xyang123@ucla.edu.
authors: Jane E
authors: JE
authors: Freedman
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Daniel
authors: D
authors: Levy
authors: From the National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (T.H., R.J., P.C., A.D.J., C.J.O., D.L.); The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (T.H., R.J., P.C., D.L.); Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (A.D.J., C.J.O.); Department of Mathematics and Statistics, Boston University, MA (J.R., M.G.L.); Department of Medicine, University of Massachusetts Medical School, Worcester (K.T., D.D.M., J.E.F.); Department of Integrative Biology and Physiology, University of California, Los Angeles (Q.M., A.B., X.Y.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M); Department of Medicine, Harvard Medical School, Harvard University, Boston, MA (R.J.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (T.L.A.); Departments of Medicine and Biochemistry, University of Ottawa, Ottawa, Ontario, Canada (R.M.); Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom (N.J.S.); National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester, United Kingdom; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany (J.E.); DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany (J.E.); Deutsches Herzzentrum München, Technische Universität München, München, Germany (H.S.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (H.S.); and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY (B.Z.).
authors: Xia
authors: X
authors: Yang
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D016014:Linear Models; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D015203:Reproducibility of Results; D049490:Systems Biology
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: coronary disease; genetics; systems biology
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