A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
Open accessAbstract
Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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Biobank analyses have provided more generalizable estimates of the relevance of genetic risk factors in the context of separate and joint effects of non-genetic factors.
“Biobank analyses have provided more generalizable estimates of the relevance of genetic risk factors in the context of the separate and joint effects of non-genetic factors81.”
From A brief history of human disease genetics (2020) · cites this paper as [81]
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Self-citationRight Ventricular Myocardial Biomarkers in Human Heart Failure
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Contribution of vasopressin to the maintenance of blood pressure during dehydration
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Self-citationLow penetrance of a SDHB mutation in a large Dutch paraganglioma family
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Upregulation of sestrin-2 expression protects against endothelial toxicity of angiotensin II
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Attenuation of Genetic Hypertension After Short-term Vasopressin V1A Receptor Antagonism
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Self-citationFamilial pheochromocytomas and paragangliomas
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Aryl hydrocarbon receptor ligands repress T-cadherin expression in vascular smooth muscle cells
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Self-citationLarge‐Scale Gene‐Centric Analysis Identifies Polymorphisms for Resistant Hypertension
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Self-citationClinical Effects of Phosphodiesterase 3A Mutations in Inherited Hypertension With Brachydactyly
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Common Genetic Variations in the Vitamin D Pathway in Relation to Blood Pressure
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Self-citationDopamine D2receptors' effects on renal inflammation are mediated by regulation of PP2A function
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Self-citationSung, Y. J., Winkler, T. W., Manning, A. K., Aschard, H., Gudnason, V. G., Harris, T. B., Smith, A. V., Boerwinkle, E., Brown, M. R., Morrison, A. C., et al. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21978 · Cited by 20 · see citing works
Self-citationCoan, P. M., Hummel, O., Diaz, A. I. G., Barrier, M., Alfazema, N., Norsworthy, P. J., Pravenec, M., Petretto, E. G., Huebner, N., & Aitman, T. J. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026716 · Cited by 14 · see citing works
Association Between a Polymorphism in CASP3 and CASP9 Genes and Ischemic Stroke
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Self-citationDuan, P., Wang, Z.-M., Liu, J., Wang, L.-N., Yang, Z., & Tu, P. (2015) · Journal of Human Hypertension · doi:10.1038/jhh.2015.13 · Cited by 8 · see citing works
Self-citationAssociation Between NEDD4L Gene and Sodium Lithium Countertransport
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Self-citationGenes, Environment, and the Heart
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Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association
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Self-citationHeart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association
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A brief history of human disease genetics
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Self-citationObjectives, design and main findings until 2020 from the Rotterdam Study
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Self-citationEvaluating the promise of inclusion of African ancestry populations in genomics
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Self-citationGene-Environment Interactions for Cardiovascular Disease
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Self-citationIs the Relationship Between Cardiovascular Disease and Alzheimer’s Disease Genetic? A Scoping Review
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Self-citation
- Authors
- Sung, Y. J., de las Fuentes, L., Winkler, T. W., Chasman, D. I., Bentley, A. R., Kraja, A. T., Ntalla, I., Warren, H. R., Guo, X., Schwander, K., Manning, A. K., Brown, M. R., Aschard, H., Feitosa, M. F., Franceschini, N., Lu, Y., Cheng, C.-Y., Sim, X., Vojinovic, D., Marten, J., Musani, S. K., Kilpeläinen, T. O., Richard, M. A., Aslibekyan, S., Bartz, T. M., Dorajoo, R., Li, C., Liu, Y., Rankinen, T., Smith, A. V., Tajuddin, S. M., Tayo, B. O., Zhao, W., Zhou, Y., Matoba, N., Sofer, T., Alver, M., Amini, M., Boissel, M., Chai, J. F., Chen, X., Divers, J., Gandin, I., Gao, C., Giulianini, F., Goel, A., Harris, S. E., Hartwig, F. P., He, M., Horimoto, A. R. V. R., Hsu, F.-C., Jackson, A. U., Kammerer, C. M., Kasturiratne, A., Komulainen, P., Kühnel, B., Leander, K., Lee, W.-J., Lin, K.-H., Luan, J., Lyytikäinen, L.-P., McKenzie, C. A., Nelson, C. P., Noordam, R., Scott, R. A., Sheu, W. H. H., Stančáková, A., Takeuchi, F., van der Most, P. J., Varga, T. V., Waken, R. J., Wang, H., Wang, Y., Ware, E. B., Weiss, S., Wen, W., Yanek, L. R., Zhang, W., Zhao, J. H., Afaq, S., Alfred, T., Amin, N., Arking, D. E., Aung, T., Barr, R. G., Bielak, L. F., Boerwinkle, E., Bottinger, E. P., Braund, P. S., Brody, J. A., Broeckel, U., Cade, B., Campbell, A., Canouil, M., Chakravarti, A., Cocca, M., Collins, F. S., Connell, J. M., de Mutsert, R., de Silva, H. J., Dörr, M., Duan, Q., Eaton, C. B., Ehret, G., Evangelou, E., Faul, J. D., Forouhi, N. G., Franco, O. H., Friedlander, Y., Gao, H., Gigante, B., Gu, C. C., Gupta, P., Hagenaars, S. P., Harris, T. B., He, J., Heikkinen, S., Heng, C.-K., Hofman, A., Howard, B. V., Hunt, S. C., Irvin, M. R., Jia, Y., Katsuya, T., Kaufman, J., Kerrison, N. D., Khor, C. C., Koh, W.-P., Koistinen, H. A., Kooperberg, C. B., Krieger, J. E., Kubo, M., Kutalik, Z., Kuusisto, J., Lakka, T. A., Langefeld, C. D., Langenberg, C., Launer, L. J., Lee, J. H., Lehne, B., Levy, D., Lewis, C. E., Li, Y., Study, L. C., Lim, S. H., Liu, C.-T., Liu, J., Liu, J., Liu, Y., Loh, M., Lohman, K. K., Louie, T., Mägi, R., Matsuda, K., Meitinger, T., Metspalu, A., Milani, L., Momozawa, Y., Mosley, Jr., Nalls, M. A., Nasri, U., O'Connell, J. R., Ogunniyi, A., Palmas, W. R., Palmer, N. D., Pankow, J. S., Pedersen, N. L., Peters, A., Peyser, P. A., Polasek, O., Porteous, D., Raitakari, O. T., Renström, F., Rice, T. K., Ridker, P. M., Robino, A., Robinson, J. G., Rose, L. M., Rudan, I., Sabanayagam, C., Salako, B. L., Sandow, K., Schmidt, C. O., Schreiner, P. J., Scott, W. R., Sever, P., Sims, M., Sitlani, C. M., Smith, B. H., Smith, J. A., Snieder, H., Starr, J. M., Strauch, K., Tang, H., Taylor, K. D., Teo, Y. Y., Tham, Y. C., Uitterlinden, A. G., Waldenberger, M., Wang, L., Wang, Y. X., Wei, W. B., Wilson, G., Wojczynski, M. K., Xiang, Y.-B., Yao, J., Yuan, J.-M., Zonderman, A. B., Becker, D. M., Boehnke, M., Bowden, D. W., Chambers, J. C., Chen, Y.-D. I., Weir, D. R., de Faire, U., Deary, I. J., Esko, T., Farrall, M., Forrester, T., Freedman, B. I., Froguel, P., Gasparini, P., Gieger, C., Horta, B. L., Hung, Y.-J., Jonas, J. B., Kato, N., Kooner, J. S., Laakso, M., Lehtimäki, T., Liang, K.-W., Magnusson, P. K. E., Oldehinkel, A. J., Pereira, A. C., Perls, T., Rauramaa, R., Redline, S., Rettig, R., Samani, N. J., Scott, J., Shu, X.-O., van der Harst, P., Wagenknecht, L. E., Wareham, N. J., Watkins, H., Wickremasinghe, A. R., Wu, T., Kamatani, Y., Laurie, C. C., Bouchard, C., Cooper, R. S., Evans, M. K., Gudnason, V., Hixson, J., Kardia, S. L. R., Kritchevsky, S. B., Psaty, B. M., van Dam, R. M., Arnett, D. K., Mook-Kanamori, D. O., Fornage, M., Fox, E. R., Hayward, C., van Duijn, C. M., Tai, E. S., Wong, T. Y., Loos, R. J. F., Reiner, A. P., Rotimi, C. N., Bierut, L. J., Zhu, X., Cupples, L. A., Province, M. A., Rotter, J. I., Franks, P. W., Rice, K., Elliott, P., Caulfield, M. J., Gauderman, W. J., Munroe, P. B., Rao, D. C., & Morrison, A. C.
- Affiliations
- Washington University in St. Louis (US)
- Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, USA
- University of Regensburg (DE)
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Queen Mary University of London (GB)
- The Lundquist Institute (US)
- Broad Institute (US)
- The University of Texas Health Science Center at Houston (US)
- Harvard University (US)
- University of North Carolina at Chapel Hill (US)
- Icahn School of Medicine at Mount Sinai (US)
- National University of Singapore (SG)
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
- Institute of Genetics and Cancer (GB)
- University of Mississippi Medical Center (US)
- University of Copenhagen (DK)
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- University of Alabama at Birmingham (US)
- University of Washington (US)
- Agency for Science, Technology and Research (SG)
- University of Georgia (US)
- Pennington Biomedical Research Center (US)
- University of Iceland (IS)
- Loyola University Chicago (US)
- University of Michigan (US)
- Boston University (US)
- RIKEN Center for Integrative Medical Sciences (JP)
- University of Tartu (EE)
- University Medical Center Groningen (NL)
- Centre National de la Recherche Scientifique (FR)
- Karolinska Institutet (SE)
- Wake Forest University Health Sciences (US)
- University of Trieste (IT)
- Centre for Human Genetics (GB)
- Universidade Federal de Pelotas (BR)
- Universidade de São Paulo (BR)
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
- University of Pittsburgh (US)
- University of Kelaniya (LK)
- Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
- Helmholtz Munich (DE)
- Tunghai University (TW)
- Taichung Veterans General Hospital (TW)
- University of Cambridge (GB)
- Fimlab (Finland) (FI)
- Tampere University (FI)
- Huazhong University of Science and Technology (CN)
- University of Leicester (GB)
- Leiden University Medical Center (NL)
- National Chung Hsing University (TW)
- University of Eastern Finland (FI)
- National Center for Global Health and Medicine (JP)
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands
- Lund University (SE)
- Beijing Tongren Hospital (CN)
- Universität Greifswald (DE)
- Vanderbilt University (US)
- Johns Hopkins University (US)
- Ealing Hospital (GB)
- MRC Centre for Environment and Health (GB)
- Erasmus MC (NL)
- Columbia University Irving Medical Center (US)
- Baylor College of Medicine (US)
- Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY, USA
- Medical College of Wisconsin (US)
- University of Dundee (GB)
- Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
- Universitätsmedizin Greifswald (DE)
- Brown University (US)
- MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK
- Hadassah Medical Center (IL)
- Singapore National Eye Center (SG)
- University of Edinburgh (GB)
- Tulane University (US)
- Georgetown University (US)
- University of Utah (US)
- The University of Osaka (JP)
- University of Helsinki (FI)
- Fred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, WA, USA
- Institute of Social Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland
- Columbia University (US)
- University of Mississippi (US)
- Geriatrics, Medicine, University of Mississippi, Jackson, MS, USA
- University of Maryland, Baltimore (US)
- Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA
- University of Ibadan (NG)
- University of Minnesota (US)
- Department of Public Health, Department of Medicine, University of Split, Split, Croatia
- University of Turku (FI)
- University of Iowa (US)
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Shanghai Jiao Tong University (CN)
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- University of the West Indies (JM)
- Tri-Service General Hospital (TW)
- China Medical University (TW)
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen RB, The Netherlands
- Kaiser Permanente Washington Health Research Institute (US)
- Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore
- University of Kentucky (US)
- University of Southern California (US)
- Corresponding author
- Sung, Yun Ju
- ORCID
- Winkler, Thomas W
- Chasman, Daniel I
- Bentley, Amy R
- Warren, Helen R
- Guo, Xiuqing
- Schwander, Karen
- Manning, Alisa K
- Aschard, Hugues
- Feitosa, Mary F
- Franceschini, Nora
- Lu, Yingchang
- Cheng, Ching-Yu
- Sim, Xueling
- Marten, Jonathan
- Kilpeläinen, Tuomas O
- Richard, Melissa A
- Aslibekyan, Stella
- Bartz, Traci M
- Dorajoo, Rajkumar
- Li, Changwei
- Smith, Albert Vernon
- Tajuddin, Salman M
- Tayo, Bamidele O
- Zhao, Wei
- Zhou, Yanhua
- Matoba, Nana
- Sofer, Tamar
- Boissel, Mathilde
- Chai, Jin Fang
- Chen, Xu
- Divers, Jasmin
- Gandin, Ilaria
- Gao, Chuan
- Goel, Anuj
- Harris, Sarah E
- Hartwig, Fernando P
- He, Meian
- Hsu, Fang-Chi
- Jackson, Anne U
- Kammerer, Candace M
- Kasturiratne, Anuradhani
- Komulainen, Pirjo
- Kühnel, Brigitte
- Leander, Karin
- Lee, Wen-Jane
- Lin, Keng-Hung
- Luan, Jian’an
- Lyytikäinen, Leo-Pekka
- Nelson, Christopher P
- Noordam, Raymond
- Sheu, Wayne H H
- Takeuchi, Fumihiko
- Varga, Tibor V
- Waken, Robert J
- Wang, Heming
- Wang, Yajuan
- Ware, Erin B
- Weiss, Stefan
- Wen, Wanqing
- Yanek, Lisa R
- Zhang, Weihua
- Zhao, Jing Hua
- Amin, Najaf
- Arking, Dan E
- Aung, Tin
- Barr, R Graham
- Bielak, Lawrence F
- Boerwinkle, Eric
- Braund, Peter S
- Brody, Jennifer A
- Broeckel, Ulrich
- Cade, Brian
- Campbell, Archie
- Canouil, Mickaël
- Chakravarti, Aravinda
- Cocca, Massimiliano
- Collins, Francis S
- Dörr, Marcus
- Duan, Qing
- Eaton, Charles B
- Ehret, Georg
- Faul, Jessica D
- Forouhi, Nita G
- Franco, Oscar H
- Friedlander, Yechiel
- Gao, He
- Gigante, Bruna
- Gu, C Charles
- Gupta, Preeti
- Hagenaars, Saskia P
- Harris, Tamara B
- He, Jiang
- Heikkinen, Sami
- Heng, Chew-Kiat
- Howard, Barbara V
- Hunt, Steven C
- Irvin, Marguerite R
- Kaufman, Joel
- Kerrison, Nicola D
- Khor, Chiea Chuen
- Koh, Woon-Puay
- Koistinen, Heikki A
- Kubo, Michiaki
- Lakka, Timo A
- Langefeld, Carl D
- Langenberg, Claudia
- Launer, Lenore J
- Lee, Joseph H
- Levy, Daniel
- Lewis, Cora E
- Li, Yize
- Liu, Jianjun
- Loh, Marie
- Mägi, Reedik
- Matsuda, Koichi
- Meitinger, Thomas
- Metspalu, Andres
- Milani, Lili
- Momozawa, Yukihide
- Nalls, Mike A
- Ogunniyi, Adesola
- Palmer, Nicholette D
- Pankow, James S
- Pedersen, Nancy L
- Peters, Annette
- Peyser, Patricia A
- Porteous, David
- Raitakari, Olli T
- Rice, Treva K
- Ridker, Paul M
- Robino, Antonietta
- Robinson, Jennifer G
- Rose, Lynda M
- Rudan, Igor
- Sabanayagam, Charumathi
- Schmidt, Carsten O
- Schreiner, Pamela J
- Scott, William R
- Sitlani, Colleen M
- Smith, Blair H
- Smith, Jennifer A
- Snieder, Harold
- Starr, John M
- Strauch, Konstantin
- Tang, Hua
- Taylor, Kent D
- Tham, Yih Chung
- Uitterlinden, André G
- Wang, Ya Xing
- Wei, Wen Bin
- Wilson, Gregory
- Wojczynski, Mary K
- Xiang, Yong-Bing
- Yao, Jie
- Yuan, Jian-Min
- Zonderman, Alan B
- Becker, Diane M
- Boehnke, Michael
- Bowden, Donald W
- Chambers, John C
- Chen, Yii-Der Ida
- Weir, David R
- Deary, Ian J
- Esko, Tõnu
- Farrall, Martin
- Freedman, Barry I
- Froguel, Philippe
- Gasparini, Paolo
- Gieger, Christian
- Horta, Bernardo Lessa
- Hung, Yi-Jen
- Jonas, Jost Bruno
- Kooner, Jaspal S
- Laakso, Markku
- Lehtimäki, Terho
- Liang, Kae-Woei
- Magnusson, Patrik K E
- Oldehinkel, Albertine J
- Pereira, Alexandre C
- Perls, Thomas
- Redline, Susan
- Samani, Nilesh J
- Scott, James
- Shu, Xiao-Ou
- Wagenknecht, Lynne E
- Wareham, Nicholas J
- Watkins, Hugh
- Wu, Tangchun
- Laurie, Cathy C
- Bouchard, Claude
- Cooper, Richard S
- Evans, Michele K
- Gudnason, Vilmundur
- Hixson, James
- Kritchevsky, Stephen B
- Psaty, Bruce M
- Arnett, Donna K
- Fornage, Myriam
- Hayward, Caroline
- Tai, E Shyong
- Wong, Tien Yin
- Loos, Ruth J F
- Reiner, Alex P
- Rotimi, Charles N
- Bierut, Laura J
- Zhu, Xiaofeng
- Cupples, L Adrienne
- Province, Michael A
- Rotter, Jerome I
- Franks, Paul W
- Rice, Kenneth
- Elliott, Paul
- Caulfield, Mark J
- Munroe, Patricia B
- Rao, Dabeeru C
- Morrison, Alanna C
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-04-10
- Volume
- 28
- Issue
- 15
- Pages
- 2615-2633
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC6644157
- OpenAlex
- W2937482092
- Cited by
- 43
- References
- 111
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 1
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Civil War Book Review (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- IRIS (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (R01HL118305)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- blood pressure, pulse pressure, mean arterial pressure, gene-smoking interaction, cigarette smoking, hypertension, genetic loci, multi-ancestry genome-wide association, African ancestry, SLC26A7, AVPR1A, caspase-9, CSMD1, lifestyle factors
- MeSH terms
- Sulfate Transporters, Adolescent, Adult, Aged, Aged, 80 and over, Blood Pressure, Ethnicity, Female, Humans, Hypertension, Male, Membrane Proteins, Middle Aged, Polymorphism, Genetic, Smoking, Receptors, Vasopressin, Antiporters, Tumor Suppressor Proteins, Racial Groups, Caspase 9, Genome-Wide Association Study, Young Adult, Gene-Environment Interaction, Arterial Pressure
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