Evidence map›Paper›PMID 25533967›Full record

ArticleCirculation2015

Integromic analysis of genetic variation and gene expression identifies networks for cardiovascular disease phenotypes.

Chen Yao, Brian H Chen, Roby Joehanes, Burcak Otlu, Xiaoling Zhang, Chunyu Liu, Tianxiao Huan, Oznur Tastan, L Adrienne Cupples, James B Meigs and 7 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03225183 (An RNA Sequencing Study in the Framingham Heart Study Third Generation Cohort Exam 2), which is not on this map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
7.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03225183 completednot on this mapstarted 2017, after this paper: background citation

An RNA Sequencing Study in the Framingham Heart Study Third Generation Cohort Exam 2

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2017 to 2019Enrolled1,700ConditionsCardiovascular Disease, Hypertension
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 71 citations in OpenAlex.

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  8. Genetic susceptibility loci forFrontiers in immunology · 2022
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  13. Frontiers in genetics · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 2 countries.

Chen YaoFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Brian H ChenFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Roby JoehanesFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Burcak OtluFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Xiaoling ZhangFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Chunyu LiuFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Tianxiao HuanFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Oznur TastanFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
L Adrienne CupplesFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
James B MeigsFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Caroline S FoxFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Jane E FreedmanFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Paul CourchesneFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Christopher J O'DonnellFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Peter J MunsonFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Sunduz KelesFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
Daniel LevyFrom the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.). LevyD@nih.gov.
Bilkent University · TRHarvard University · USMiddle East Technical University · TRUniversity of Massachusetts Chan Medical School · USUniversity of Wisconsin–Madison · US

Funding

Framingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1M
Translational Research Skills Development CoreU54HL112311 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S, ZIMMERMAN, GUY A. · 2012 to 2016
$12.9M
Genomic Epidemiology of Cardiovascular DiseaseZIAHL006002 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2009 to 2015
$8.0M
Common Genetic Variation and Quantitative Diabetes TraitsR01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2008 to 2014
$5.0M
Statistical Methods for the Analysis of ChlP-chip DataR01HG003747 · NHGRI · UNIVERSITY OF WISCONSIN-MADISON · PI KELES, SUNDUZ · 2007 to 2024
$4.8M
Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
Racial and Ethnic Diversity in Human Extracellular RNAU01HL126495 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FREEDMAN, JANE E, GERSTEIN, MARK BENDER · 2014 to 2018
$3.4M
Gene Expression for Functional Genomics in Human PopulationsZIAHL006175 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.2M
Functional Genetic Variation Underlying Cardiovascular Genomic EpidemiologyZIAHL006173 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.0M
Epidemiology of Precursors to Type 2 DiabetesK24DK080140 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2007 to 2016
$1.9M
Statistical Methods For Annotating Repetitive Genomic Regions Through ENCODE-deriU01HG007019 · NHGRI · UNIVERSITY OF WISCONSIN-MADISON · PI BRESNICK, EMERY H, DEWEY, COLIN NOEL · 2012 to 2015
$1.5M
Extracellular RNAs: Biomarkers for Cardiovascular Risk and DiseaseUH2TR000921 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FREEDMAN, JANE E · 2013 to 2014
$1.0M
Intramural NIH HHSNCATS NIH HHS UH2 TR000921NHGRI NIH HHS R01 HG003747NHGRI NIH HHS U01 HG007019NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS U01 HL126495NHLBI NIH HHS U54 HL112311NIDDK NIH HHS K24 DK080140NIDDK NIH HHS R01 DK078616NIDDK NIH HHS U01 DK078616
6 · The paper itself

Abstract

backgroundCardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. METHODS AND

resultsWe built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P≤5×10(-8)) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes.

conclusionsUsing a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD.

Indexed as

AdultCardiovascular DiseasesChromosome MappingCoronary Artery DiseaseDiabetes Mellitus, Type 1FemaleGene ExpressionGene Regulatory NetworksGenetic VariationGenome-Wide Association StudyHumansLDL-Receptor Related Protein-Associated ProteinLipoproteins, HDLLipoproteins, LDLMalePhenotypeLDL-Receptor Related Protein-Associated ProteinLipoproteins, HDLLipoproteins, LDLcardiovascular diseasegene expression/regulation networkgenetic variation

Identifiers

PMID25533967
PMCPMC4369387
OpenAlexW1984794443

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.