Meta-Analysis

. 2016 Oct;48(10):1162-70.

doi: 10.1038/ng.3660. Epub 2016 Sep 12.

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

Chunyu Liu^{1

2

3}, Aldi T Kraja⁴, Jennifer A Smith⁵, Jennifer A Brody⁶, Nora Franceschini⁷, Joshua C Bis⁶, Kenneth Rice⁸, Alanna C Morrison⁹, Yingchang Lu¹⁰, Stefan Weiss^{11

12}, Xiuqing Guo¹³, Walter Palmas¹⁴, Lisa W Martin¹⁵, Yii-Der Ida Chen¹³, Praveen Surendran¹⁶, Fotios Drenos^{17

18}, James P Cook^{19

20}, Paul L Auer²¹, Audrey Y Chu^{1

3

22}, Ayush Giri²³, Wei Zhao⁵, Johanna Jakobsdottir²⁴, Li-An Lin²⁵, Jeanette M Stafford²⁶, Najaf Amin²⁷, Hao Mei²⁸, Jie Yao¹³, Arend Voorman²⁹; CHD Exome+ Consortium; ExomeBP Consortium; GoT2DGenes Consortium; T2D-GENES Consortium; Martin G Larson^{1

2

30}, Megan L Grove⁹, Albert V Smith^{24

31}, Shih-Jen Hwang^{1

3}, Han Chen³², Tianxiao Huan^{1

3}, Gulum Kosova^{33

34}, Nathan O Stitziel³⁵, Sekar Kathiresan^{33

34}, Nilesh Samani^{36

37}, Heribert Schunkert^{38

39}, Panos Deloukas^{40

41}; Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia; Man Li⁴², Christian Fuchsberger⁴³, Cristian Pattaro⁴³, Mathias Gorski⁴⁴; CKDGen Consortium; Charles Kooperberg⁴⁵, George J Papanicolaou⁴⁶, Jacques E Rossouw⁴⁶, Jessica D Faul⁴⁷, Sharon L R Kardia⁵, Claude Bouchard⁴⁸, Leslie J Raffel⁴⁹, André G Uitterlinden^{50

51}, Oscar H Franco⁵⁰, Ramachandran S Vasan^{1

52}, Christopher J O'Donnell^{1

53

54

55}, Kent D Taylor¹³, Kiang Liu⁵⁶, Erwin P Bottinger¹⁰, Omri Gottesman¹⁰, E Warwick Daw⁴, Franco Giulianini²², Santhi Ganesh^{57

58}, Elias Salfati⁵⁹, Tamara B Harris⁶⁰, Lenore J Launer⁶¹, Marcus Dörr^{11

62}, Stephan B Felix^{11

62}, Rainer Rettig^{11

63}, Henry Völzke^{11

64

65}, Eric Kim¹³, Wen-Jane Lee⁶⁶, I-Te Lee^{67

68

69}, Wayne H-H Sheu^{67

68

70

71}, Krystal S Tsosie²³, Digna R Velez Edwards^{23

72}, Yongmei Liu⁷³, Adolfo Correa⁷⁴, David R Weir⁴⁷, Uwe Völker^{11

12}, Paul M Ridker^{22

75}, Eric Boerwinkle⁹, Vilmundur Gudnason^{24

31}, Alexander P Reiner⁷⁶, Cornelia M van Duijn²⁷, Ingrid B Borecki⁴, Todd L Edwards^{23

77}, Aravinda Chakravarti⁵⁹, Jerome I Rotter^{13

78}, Bruce M Psaty^{6

76

79

80}, Ruth J F Loos^{10

80}, Myriam Fornage²⁵, Georg B Ehret^{59

81}, Christopher Newton-Cheh^{33

34

82}, Daniel Levy^{1

3}, Daniel I Chasman^{22

75}

Affiliations

¹ Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, USA.
² Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA.
³ Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
⁴ Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
⁵ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁷ Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁸ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
⁹ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston Texas, USA.
¹⁰ Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹¹ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
¹² Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
¹³ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
¹⁴ Division of General Medicine, Columbia University Medical Center, New York, New York, USA.
¹⁵ George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
¹⁶ Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁷ Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
¹⁸ MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
¹⁹ Department of Biostatistics, University of Liverpool, Liverpool, UK.
²⁰ Department of Health Sciences, University of Leicester, Leicester, UK.
²¹ Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
²² Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
²³ Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁴ Icelandic Heart Association, Kopavogur, Iceland.
²⁵ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
²⁶ Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
²⁷ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
²⁸ Department of Data Science, School of Population Health, University of Mississippi Medical Center, Jackson, Mississippi, USA.
²⁹ Bill and Melinda Gates Foundation, Seattle, Washington, USA.
³⁰ Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA.
³¹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
³² Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
³³ Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, Massachusetts, USA.
³⁵ Division of Cardiology, Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁶ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
³⁷ NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
³⁸ Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
³⁹ DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany.
⁴⁰ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
⁴¹ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴² Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
⁴³ Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated with the University of Lübeck, Lübeck, Germany).
⁴⁴ Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
⁴⁵ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁴⁶ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
⁴⁷ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
⁴⁸ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
⁴⁹ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁵⁰ Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
⁵¹ Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
⁵² Department of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
⁵³ Cardiology Section, Department of Medicine, Boston Veterans Administration Healthcare, Boston, Massachusetts, USA.
⁵⁴ Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁵⁵ Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
⁵⁶ Northwestern University School of Medicine, Chicago, Illinois, USA.
⁵⁷ Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
⁵⁸ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁵⁹ Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶⁰ Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
⁶¹ Neuroepidemiology Section, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
⁶² Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
⁶³ Institute of Physiology, University of Greifswald, Greifswald, Germany.
⁶⁴ DZD (German Center for Diabetes Research), site Greifswald, Greifswald, Germany.
⁶⁵ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁶⁶ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶⁷ Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶⁸ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁶⁹ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁷⁰ Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan.
⁷¹ School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁷² Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷³ Epidemiology and Prevention Center for Genomics and Personalized Medicine Research, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.
⁷⁴ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
⁷⁵ Harvard Medical School, Boston, Massachusetts, USA.
⁷⁶ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
⁷⁷ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷⁸ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA.
⁷⁹ Department of Health Services, University of Washington, Seattle, Washington, USA.
⁸⁰ Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸¹ Cardiology, Geneva University Hospitals, Geneva, Switzerland.
⁸² Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

PMID: 27618448
PMCID: PMC5320952
DOI: 10.1038/ng.3660

Meta-Analysis

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

Chunyu Liu et al. Nat Genet. 2016 Oct.

. 2016 Oct;48(10):1162-70.

doi: 10.1038/ng.3660. Epub 2016 Sep 12.

Authors

Affiliations

¹ Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, USA.
² Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA.
³ Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
⁴ Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
⁵ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
⁷ Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁸ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
⁹ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston Texas, USA.
¹⁰ Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹¹ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
¹² Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
¹³ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
¹⁴ Division of General Medicine, Columbia University Medical Center, New York, New York, USA.
¹⁵ George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
¹⁶ Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁷ Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
¹⁸ MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.
¹⁹ Department of Biostatistics, University of Liverpool, Liverpool, UK.
²⁰ Department of Health Sciences, University of Leicester, Leicester, UK.
²¹ Joseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
²² Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
²³ Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁴ Icelandic Heart Association, Kopavogur, Iceland.
²⁵ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
²⁶ Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
²⁷ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
²⁸ Department of Data Science, School of Population Health, University of Mississippi Medical Center, Jackson, Mississippi, USA.
²⁹ Bill and Melinda Gates Foundation, Seattle, Washington, USA.
³⁰ Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA.
³¹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
³² Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
³³ Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, Massachusetts, USA.
³⁵ Division of Cardiology, Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁶ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
³⁷ NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
³⁸ Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
³⁹ DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany.
⁴⁰ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
⁴¹ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴² Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
⁴³ Center for Biomedicine, European Academy of Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated with the University of Lübeck, Lübeck, Germany).
⁴⁴ Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
⁴⁵ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁴⁶ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
⁴⁷ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
⁴⁸ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
⁴⁹ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁵⁰ Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
⁵¹ Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
⁵² Department of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
⁵³ Cardiology Section, Department of Medicine, Boston Veterans Administration Healthcare, Boston, Massachusetts, USA.
⁵⁴ Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁵⁵ Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
⁵⁶ Northwestern University School of Medicine, Chicago, Illinois, USA.
⁵⁷ Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
⁵⁸ Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁵⁹ Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁶⁰ Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
⁶¹ Neuroepidemiology Section, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.
⁶² Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
⁶³ Institute of Physiology, University of Greifswald, Greifswald, Germany.
⁶⁴ DZD (German Center for Diabetes Research), site Greifswald, Greifswald, Germany.
⁶⁵ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁶⁶ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶⁷ Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶⁸ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁶⁹ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁷⁰ Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan.
⁷¹ School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁷² Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷³ Epidemiology and Prevention Center for Genomics and Personalized Medicine Research, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.
⁷⁴ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
⁷⁵ Harvard Medical School, Boston, Massachusetts, USA.
⁷⁶ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
⁷⁷ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷⁸ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA.
⁷⁹ Department of Health Services, University of Washington, Seattle, Washington, USA.
⁸⁰ Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸¹ Cardiology, Geneva University Hospitals, Geneva, Switzerland.
⁸² Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

PMID: 27618448
PMCID: PMC5320952
DOI: 10.1038/ng.3660

Abstract

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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Figures

**Figure 1. Overall study design**
In the discovery phase, single variant and gene-based analyses were performed for systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, and hypertension among 146,562 individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus (CHARGE+) Exome Chip Blood Pressure Consortium. Fifteen variants were significant (P<3.4×10⁻⁷) and 62 displayed P<1×10⁻⁵. In the follow-up phase, meta-analysis was performed for 77 variants with results from 180,726 individuals from the CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D–GENES consortium.

**Figure 2. *NPR1* Gene: Low-frequency and rare variants associated in aggregate with mean arterial pressure**
The *NPR1* protein (1,061 amino acids) is comprised of three domains: extracellular domain, kinase homology domain, and guanylate cyclase domain. The effects of the 14 low-frequency and rare variants after adjustment for age, age², sex, and body mass index on mean arterial pressure are shown for higher (tan) or lower (purple) values in mm Hg; dot area is proportional to the number of minor allele carriers. The minor allele of rs35479618 (MAF ∼ 0.012, E967K), was carried by 3,164 participants. The minor allele of rs201787421 (MAF ∼ 2.6×10⁻⁵ R782Q), was carried by 5 participants.

**Figure 3. *DBH* Gene: Rare variants associated in aggregate with mean arterial pressure**
The *DBH* protein (617 amino acids) contains the dopamine β-monooxygenase N-terminal (DOMON) domain, the catalytic core (the Cu_H and Cu_M domains) and the C-terminal (C–T) domain. The effects of the 27 rare variants after adjustment for age, age², sex, and body mass index on mean arterial pressure are shown for higher (tan) or lower (purple) values in mm Hg. The minor allele of rs74853476 (MAF ∼ 0.0015), a splicing variant, was carried by 291 participants. The minor allele of rs201681337 (MAF ∼ 7.9×10⁻⁵, A301T), was carried by 4 participants.

See this image and copyright information in PMC

Comment in

Genetics: Genetic factors in the regulation of blood pressure.
Palmer ND, Freedman BI. Palmer ND, et al. Nat Rev Nephrol. 2016 Dec;12(12):716-717. doi: 10.1038/nrneph.2016.150. Epub 2016 Oct 17. Nat Rev Nephrol. 2016. PMID: 27748393 No abstract available.

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

Comment in

References

Methods-only References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Miscellaneous