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Research Article

Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation In Vivo

  • M. Kamran Ikram equal contributor,

    equal contributor Contributed equally to this work with: M. Kamran Ikram, Sim Xueling, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Sim Xueling equal contributor,

    equal contributor Contributed equally to this work with: M. Kamran Ikram, Sim Xueling, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt

    Affiliation: Centre for Molecular Epidemiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

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  • Richard A. Jensen equal contributor,

    equal contributor Contributed equally to this work with: M. Kamran Ikram, Sim Xueling, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt

    Affiliations: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America

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  • Mary Frances Cotch equal contributor,

    equal contributor Contributed equally to this work with: M. Kamran Ikram, Sim Xueling, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt

    Affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Alex W. Hewitt equal contributor,

    equal contributor Contributed equally to this work with: M. Kamran Ikram, Sim Xueling, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt

    Affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

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  • M. Arfan Ikram,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Jie Jin Wang,

    Affiliations: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia, Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia

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  • Ronald Klein,

    Affiliation: Department of Ophthalmology and Visual Science, University of Wisconsin, Madison, Wisconsin, United States of America

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  • Barbara E. K. Klein,

    Affiliation: Department of Ophthalmology and Visual Science, University of Wisconsin, Madison, Wisconsin, United States of America

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  • Monique M. B. Breteler,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Ning Cheung,

    Affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

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  • Gerald Liew,

    Affiliation: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia

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  • Paul Mitchell,

    Affiliation: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia

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  • Andre G. Uitterlinden,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Fernando Rivadeneira,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Albert Hofman,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Paulus T. V. M. de Jong,

    Affiliations: Netherlands Institute of Neuroscience, Amsterdam, The Netherlands, Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands

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  • Cornelia M. van Duijn,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

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  • Linda Kao,

    Affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America

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  • Ching-Yu Cheng,

    Affiliations: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, Department of Ophthalmology, National Yang-Ming University School of Medicine, Taipei, Taiwan

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  • Albert Vernon Smith,

    Affiliations: Icelandic Heart Association, Kopavogur, Iceland, Faculty of Medicine, University of Iceland, Reykjavik, Iceland

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  • Nicole L. Glazer,

    Affiliations: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America, Department of Medicine, University of Washington, Seattle, Washington, United States of America

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  • Thomas Lumley,

    Affiliations: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America, Department of Biostatistics, University of Washington, Seattle, Washington, United States of America

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  • Barbara McKnight,

    Affiliations: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America, Department of Biostatistics, University of Washington, Seattle, Washington, United States of America

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  • Bruce M. Psaty,

    Affiliations: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America, Department of Medicine, University of Washington, Seattle, Washington, United States of America, Department of Health Services, University of Washington, Seattle, Washington, United States of America, Center for Health Studies, Group Health, Seattle, Washington, United States of America

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  • Fridbert Jonasson,

    Affiliations: Department of Ophthalmology, University of Iceland, Reykjavik, Iceland, Department of Ophthalmology, Landspitalinn University Hospital, Reykjavik, Iceland

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  • Gudny Eiriksdottir,

    Affiliation: Icelandic Heart Association, Kopavogur, Iceland

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  • Thor Aspelund,

    Affiliations: Icelandic Heart Association, Kopavogur, Iceland, Department of Statistics, University of Iceland, Reykjavik, Iceland

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  • Global BPgen Consortium,
  • Tamara B. Harris,

    Affiliation: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Lenore J. Launer,

    Affiliation: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Kent D. Taylor,

    Affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

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  • Xiaohui Li,

    Affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

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  • Sudha K. Iyengar,

    Affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America

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  • Quansheng Xi,

    Affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America

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  • Theru A. Sivakumaran,

    Affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America

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  • David A. Mackey,

    Affiliations: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia, Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia

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  • Stuart MacGregor,

    Affiliation: Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia

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  • Nicholas G. Martin,

    Affiliation: Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia

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  • Terri L. Young,

    Affiliation: Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, United States of America

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  • Josh C. Bis,

    Affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America

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  • Kerri L. Wiggins,

    Affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America

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  • Susan R. Heckbert,

    Affiliations: Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America, Center for Health Studies, Group Health, Seattle, Washington, United States of America

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  • Christopher J. Hammond,

    Affiliation: Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom

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  • Toby Andrew,

    Affiliation: Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom

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  • Samantha Fahy,

    Affiliation: Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom

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  • John Attia,

    Affiliations: School of Biomedical Sciences, University of Newcastle, Callaghan, Australia, Hunter Medical Research Institute, Newcastle, Australia

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  • Elizabeth G. Holliday,

    Affiliations: School of Biomedical Sciences, University of Newcastle, Callaghan, Australia, Hunter Medical Research Institute, Newcastle, Australia

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  • Rodney J. Scott,

    Affiliations: School of Biomedical Sciences, University of Newcastle, Callaghan, Australia, Hunter Medical Research Institute, Newcastle, Australia

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  • F. M. Amirul Islam,

    Affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

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  • Jerome I. Rotter,

    Affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

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  • Annie K. McAuley,

    Affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

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  • Eric Boerwinkle,

    Affiliation: Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America

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  • E. Shyong Tai ,

    Affiliations: Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    These authors also contributed equally to this work.

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  • Vilmundur Gudnason ,

    Affiliations: Icelandic Heart Association, Kopavogur, Iceland, Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    These authors also contributed equally to this work.

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  • David S. Siscovick ,

    Affiliations: Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America, Department of Medicine, University of Washington, Seattle, Washington, United States of America

    These authors also contributed equally to this work.

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  • Johannes R. Vingerling ,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands

    These authors also contributed equally to this work.

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  • Tien Y. Wong mail

    ophwty@nus.edu.sg

    Affiliations: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia, Singapore National Eye Centre and Singapore Eye Research Institute, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    These authors also contributed equally to this work.

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  • Published: October 28, 2010
  • DOI: 10.1371/journal.pgen.1001184

About the Authors

M. Kamran Ikram, M. Arfan Ikram, Monique M. B. Breteler, Andre G. Uitterlinden, Fernando Rivadeneira, Albert Hofman, Cornelia M. van Duijn, Johannes R. Vingerling
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
M. Kamran Ikram, Johannes R. Vingerling
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands
M. Kamran Ikram
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
Sim Xueling
Centre for Molecular Epidemiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Richard A. Jensen, Nicole L. Glazer, Thomas Lumley, Barbara McKnight, Bruce M. Psaty, David S. Siscovick
Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, United States of America
Richard A. Jensen, Bruce M. Psaty, David S. Siscovick
Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
Mary Frances Cotch
Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States of America
Alex W. Hewitt, Jie Jin Wang, Ning Cheung, F. M. Amirul Islam, Annie K. McAuley, Tien Y. Wong
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
Jie Jin Wang, Gerald Liew, Paul Mitchell, David A. Mackey
Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia
Ronald Klein, Barbara E. K. Klein
Department of Ophthalmology and Visual Science, University of Wisconsin, Madison, Wisconsin, United States of America
Andre G. Uitterlinden, Fernando Rivadeneira
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Andre G. Uitterlinden
Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands
Paulus T. V. M. de Jong
Netherlands Institute of Neuroscience, Amsterdam, The Netherlands
Paulus T. V. M. de Jong
Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands
Linda Kao
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
Ching-Yu Cheng
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
Ching-Yu Cheng
Department of Ophthalmology, National Yang-Ming University School of Medicine, Taipei, Taiwan
Albert Vernon Smith, Gudny Eiriksdottir, Thor Aspelund, Vilmundur Gudnason
Icelandic Heart Association, Kopavogur, Iceland
Albert Vernon Smith, Vilmundur Gudnason
Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Nicole L. Glazer, Bruce M. Psaty, David S. Siscovick
Department of Medicine, University of Washington, Seattle, Washington, United States of America
Thomas Lumley, Barbara McKnight
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America
Bruce M. Psaty
Department of Health Services, University of Washington, Seattle, Washington, United States of America
Bruce M. Psaty, Susan R. Heckbert
Center for Health Studies, Group Health, Seattle, Washington, United States of America
Fridbert Jonasson
Department of Ophthalmology, University of Iceland, Reykjavik, Iceland
Fridbert Jonasson
Department of Ophthalmology, Landspitalinn University Hospital, Reykjavik, Iceland
Thor Aspelund
Department of Statistics, University of Iceland, Reykjavik, Iceland
Tamara B. Harris, Lenore J. Launer
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States of America
Kent D. Taylor, Xiaohui Li, Jerome I. Rotter
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
Sudha K. Iyengar, Quansheng Xi, Theru A. Sivakumaran
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America
David A. Mackey
Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia
Stuart MacGregor, Nicholas G. Martin
Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia
Terri L. Young
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, United States of America
Josh C. Bis, Kerri L. Wiggins
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America
Susan R. Heckbert
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
Christopher J. Hammond, Toby Andrew, Samantha Fahy
Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom
John Attia, Elizabeth G. Holliday, Rodney J. Scott
School of Biomedical Sciences, University of Newcastle, Callaghan, Australia
John Attia, Elizabeth G. Holliday, Rodney J. Scott
Hunter Medical Research Institute, Newcastle, Australia
Eric Boerwinkle
Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America
E. Shyong Tai
Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
E. Shyong Tai
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Tien Y. Wong
Singapore National Eye Centre and Singapore Eye Research Institute, Singapore
Tien Y. Wong
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Corresponding Author

Email: ophwty@nus.edu.sg

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: RK BEKK MMBB NC PM AGU FR AH PTVMdJ CMvD BMP FJ GE TA LJL KDT SKI CJH JIR EB VG DSS JRV TYW. Analyzed the data: MKI SX RAJ MFC AWH MAI JJW GL FR CMvD LK CYC AVS NLG TL BM TBH XL QX TAS DAM SM NGM TLY JCB KLW SRH TA SF EGH EST TYW. Wrote the paper: MKI SX RAJ MFC AWH MAI JJW RK BEKK MMBB NC GL PM AGU AH PTVMdJ LK CYC AVS NLG TL BM BMP FJ GE TA TBH LJL KDT XL SKI QX TAS DAM SM NGM TLY CJH TA SF JA EGH RJS FMAI JIR AKM EB EST VG DSS JRV TYW.