Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Chunyu Liu; Aldi T Kraja; Jennifer A Smith; Jennifer A Brody; Nora Franceschini; Joshua C Bis; Kenneth Rice; Alanna C Morrison; Yingchang Lu; Stefan Weiss; Xiuqing Guo; Walter Palmas; Lisa W Martin; Yii-Der Ida Chen; Praveen Surendran; Fotios Drenos; James P Cook; Paul L Auer; Audrey Y Chu; Ayush Giri; Wei Zhao; Johanna Jakobsdottir; Li-An Lin; Jeanette M Stafford; Najaf Amin; Hao Mei; Jie Yao; Arend Voorman; Martin G Larson; Megan L Grove; Albert V Smith; Shih-Jen Hwang; Han Chen; Tianxiao Huan; Gulum Kosova; Nathan O Stitziel; Sekar Kathiresan; Nilesh Samani; Heribert Schunkert; Panos Deloukas; Man Li; Christian Fuchsberger; Cristian Pattaro; Mathias Gorski; Charles Kooperberg; George J Papanicolaou; Jacques E Rossouw; Jessica D Faul; Sharon L R Kardia; Claude Bouchard; Leslie J Raffel; André G Uitterlinden; Oscar H Franco; Ramachandran S Vasan; Christopher J O'Donnell; Kent D Taylor; Kiang Liu; Erwin P Bottinger; Omri Gottesman; E Warwick Daw; Franco Giulianini; Santhi Ganesh; Elias Salfati; Tamara B Harris; Lenore J Launer; Marcus Dörr; Stephan B Felix; Rainer Rettig; Henry Völzke; Eric Kim; Wen-Jane Lee; I-Te Lee; Wayne H-H Sheu; Krystal S Tsosie; Digna R Velez Edwards; Yongmei Liu; Adolfo Correa; David R Weir; Uwe Völker; Paul M Ridker; Eric Boerwinkle; Vilmundur Gudnason; Alexander P Reiner; Cornelia M van Duijn; Ingrid B Borecki; Todd L Edwards; Aravinda Chakravarti; Jerome I Rotter; Bruce M Psaty; Ruth J F Loos; Myriam Fornage; Georg B Ehret; Christopher Newton-Cheh; Daniel Levy; Daniel I Chasman; Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia

doi:10.1038/ng.3660

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Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Journal article

Peer reviewed

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Chunyu Liu, Aldi T Kraja, Jennifer A Smith, Jennifer A Brody, Nora Franceschini, Joshua C Bis, Kenneth Rice, Alanna C Morrison, Yingchang Lu, Stefan Weiss, …

Nature genetics, Vol.48(10), pp.1162-1170

01/10/2016

DOI: https://doi.org/10.1038/ng.3660

PMCID: PMC5320952

PMID: 27618448

Abstract

Blood Pressure - genetics

Exome

Genetic Variation

Genome, Human

Genome-Wide Association Study

Genotype

Humans

Hypertension - genetics

Oligonucleotide Array Sequence Analysis

Polymorphism, Single Nucleotide

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.

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Title: Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci
Creators - without role: Chunyu Liu - National Heart Lung and Blood Institute
Aldi T Kraja - Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA
Jennifer A Smith - University of Michigan–Ann Arbor
Jennifer A Brody - University of Washington
Nora Franceschini - University of North Carolina at Chapel Hill
Joshua C Bis - University of Washington
Kenneth Rice - University of Washington
Alanna C Morrison - The University of Texas Health Science Center at Houston
Yingchang Lu - Icahn School of Medicine at Mount Sinai
Stefan Weiss - University of Greifswald
Xiuqing Guo - The Lundquist Institute
Walter Palmas - Columbia University Irving Medical Center
Lisa W Martin - George Washington University
Yii-Der Ida Chen - The Lundquist Institute
Praveen Surendran - University of Cambridge
Fotios Drenos - University of Bristol
James P Cook - University of Leicester
Paul L Auer - University of Wisconsin–Milwaukee
Audrey Y Chu - Brigham and Women's Hospital
Ayush Giri - Vanderbilt University Medical Center
Wei Zhao - University of Michigan–Ann Arbor
Johanna Jakobsdottir - Icelandic Heart Association
Li-An Lin - The University of Texas Health Science Center at Houston
Jeanette M Stafford - Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Najaf Amin - Erasmus MC
Hao Mei - University of Mississippi Medical Center
Jie Yao - The Lundquist Institute
Arend Voorman - Bill & Melinda Gates Foundation
Martin G Larson - Boston University
Megan L Grove - The University of Texas Health Science Center at Houston
Albert V Smith - University of Iceland
Shih-Jen Hwang - National Heart Lung and Blood Institute
Han Chen - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
Tianxiao Huan - National Heart Lung and Blood Institute
Gulum Kosova - Broad Institute
Nathan O Stitziel - Division of Cardiology, Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
Sekar Kathiresan - Broad Institute
Nilesh Samani - NIHR Leicester Cardiovascular Biomedical Research Unit
Heribert Schunkert - DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany
Panos Deloukas - Queen Mary University of London
Man Li - Johns Hopkins University
Christian Fuchsberger - University of Lübeck
Cristian Pattaro - University of Lübeck
Mathias Gorski - University of Regensburg
Charles Kooperberg - Hutchinson
George J Papanicolaou - National Heart Lung and Blood Institute
Jacques E Rossouw - National Heart Lung and Blood Institute
Jessica D Faul - University of Michigan–Ann Arbor
Sharon L R Kardia - University of Michigan–Ann Arbor
Claude Bouchard - Louisiana State University System
Leslie J Raffel - Cedars-Sinai Medical Center
André G Uitterlinden - Erasmus MC
Oscar H Franco - Erasmus MC
Ramachandran S Vasan - Boston University School of Medicine
Christopher J O'Donnell - Harvard Medical School
Kent D Taylor - The Lundquist Institute
Kiang Liu - Northwestern University
Erwin P Bottinger - Icahn School of Medicine at Mount Sinai
Omri Gottesman - Icahn School of Medicine at Mount Sinai
E Warwick Daw - Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA
Franco Giulianini - Brigham and Women's Hospital
Santhi Ganesh - University of Michigan–Ann Arbor
Elias Salfati - Johns Hopkins University School of Medicine
Tamara B Harris - National Institute on Aging
Lenore J Launer - National Institute on Aging
Marcus Dörr - Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
Stephan B Felix - Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
Rainer Rettig - University of Greifswald
Henry Völzke - Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
Eric Kim - The Lundquist Institute
Wen-Jane Lee - Taichung Veterans General Hospital
I-Te Lee - Chung Shan Medical University
Wayne H-H Sheu - National Defense Medical Center
Krystal S Tsosie - Vanderbilt University Medical Center
Digna R Velez Edwards - Vanderbilt University Medical Center
Yongmei Liu - Atrium Health Wake Forest Baptist
Adolfo Correa - University of Mississippi Medical Center
David R Weir - University of Michigan–Ann Arbor
Uwe Völker - University of Greifswald
Paul M Ridker - Harvard Medical School
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Vilmundur Gudnason - University of Iceland
Alexander P Reiner - University of Washington
Cornelia M van Duijn - Erasmus MC
Ingrid B Borecki - Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA
Todd L Edwards - Vanderbilt University Medical Center
Aravinda Chakravarti - Johns Hopkins University School of Medicine
Jerome I Rotter - The Lundquist Institute
Bruce M Psaty - Icahn School of Medicine at Mount Sinai
Ruth J F Loos - Icahn School of Medicine at Mount Sinai
Myriam Fornage - The University of Texas Health Science Center at Houston
Georg B Ehret - Cardiology, Geneva University Hospitals, Geneva, Switzerland
Christopher Newton-Cheh - Massachusetts General Hospital
Daniel Levy - National Heart Lung and Blood Institute
Daniel I Chasman - Harvard Medical School
Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia
Publication Details: Nature genetics, Vol.48(10), pp.1162-1170
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Identifiers: 9938224808331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article