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A genome-wide scan for primary open-angle glaucoma (POAG): the Barbados Family Study of Open-Angle Glaucoma

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Abstract

Primary open-angle glaucoma (POAG) is characterized by damage to the optic nerve with associated loss of vision. Six named genetic loci have been identified as contributing to POAG susceptibility by genetic linkage analysis of mostly Caucasian families, and two of the six causative genes have been identified. The Barbados Family Study of Open-Angle Glaucoma (BFSG) was designed to evaluate the genetic component of POAG in a population of African descent. A genome-wide scan was performed on 1327 individuals from 146 families in Barbados, West Indies. Linkage results were based on models and parameter estimates derived from a segregation analysis of these families, and on model-free analyses. Two-point LOD scores >1.0 were identified on chromosomes 1, 2, 9, 10, 11, and 14, with increased multipoint LOD scores being found on chromosomes 2, 10, and 14. Fine mapping was subsequently carried out and indicated that POAG may be linked to intervals on chromosome 2q between D2S2188 and D2S2178 and chromosome 10p between D10S1477 and D10S601. Heterogeneity testing strongly supports linkage for glaucoma to at least one of these regions and suggests possible linkages to both. Although TIGR/myocilin and optineurin mutations have been shown to be causally linked to POAG in other populations, findings from this study do not support either of these as causative genes in an Afro-Caribbean population known to have relatively high rates of POAG.

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Acknowledgements

We wish to thank the BFSG participants, the Queen Elizabeth Hospital, and the Ministry of Health, Barbados, West Indies for their role in the study. In addition, we are grateful to the Computational Methods and Algorithms Group in the Division of Computational Bioscience at the Center for Information Technology of the National Institutes of Health (NIH) for providing high-performance computational resources for this study. We should also like to acknowledge Dr. Edwin Stone at the University of Iowa for his genotyping assistance in a sample of participants, and the expert technical assistance of Ms. Chalani De Silva at the NIH and her student assistants, Ms. Chamari De Silva and Catalina Teba.

The BFSG Study Group

M. Christina Leske, MD, MPH (Principal Investigator)

Coordinating Center—University at Stony Brook, Stony Brook, NY

M.C. Leske, MD, MPH; Barbara Nemesure, PhD; Qimei He, PhD; Suh-Yuh Wu, MS; Nancy Mendell, PhD; Lixin Jiang, MS; Kasthuri Sarma; Koumudi Manthani.

Data Collection Center—Ministry of Health, Bridgetown, Barbados, West Indies

Anselm Hennis, MRCP (UK), PhD; Ann Bannister, MB, BS, DO, MRCOphth (UK); Muthu Thangaraj, MB, BS, DO; Rajiv Luthra, MD, MPH; Coreen Barrow; Anthanette Holder.

Fundus Photography Center—The Johns Hopkins University, Baltimore, MD

Andrew P. Schachat, MD; Judith A. Alexander; Deborah Phillips; Reva Ward-Strozykowski.

Laboratory Center—The National Eye Institute, Bethesda, MD

James Fielding Hejtmancik, MD, PhD; Joy Redman, MS; Xiadong Jiao, PhD.

Local Advisory Group—Trevor Hassell, MBBS, FRCP, FACC, GCM (Department of Cardiology) and Henry Fraser, FACP, FRCP (UK), PhD, GCM (Chronic Diseases Research Centre) School of Clinical Medicine and Research, University of the West Indies; Clive Gibbons, FRCS (Ed), FRCP, FCOph (UK) (Department of Ophthalmology) Queen Elizabeth Hospital, Barbados, West Indies.

Author information

Author notes

  1. Joy Redman

    Present address: Quest Diagnostics, San Juan Capistrano, California, USA

  2. Henri-Jean Garchon

    Present address: Universit Réné Descartes Paris V and Service d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris, France

Authors and Affiliations

  1. Department of Preventive Medicine, School of Medicine, Stony Brook University, Stony Brook, New York 11794–8036, USA

    Barbara Nemesure, Qimei He, M. Cristina Leske, Suh-Yuh Wu, Anselm Hennis & Barbados Family Study Group

  2. Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

    Xiaodong Jiao, Joy Redman, Fielding Hejtmancik & Barbados Family Study Group

  3. School of Clinical Medicine and Research, University of the West Indies, Barbados, West Indies

    Anselm Hennis

  4. Ministry of Health, Barbados, West Indies

    Anselm Hennis & Barbados Family Study Group

  5. Department of Applied Mathematics and Statistics, Stony Brook University, College of Arts and Sciences, Stony Brook, New York, USA

    Nancy Mendell

  6. INSERM Unit 25, Hôpital Necker, 161 Rue de Sèvres, 75743 , Paris cedex 15, France

    Henri-Jean Garchon

  7. Information Engineering Branch, National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

    Richa Agarwala

  8. Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

    Alejandro A. Schäffer

  9. , The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Barbados Family Study Group

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  1. Barbara Nemesure
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  2. Xiaodong Jiao
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  3. Qimei He
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  8. Joy Redman
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  11. Alejandro A. Schäffer
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Correspondence to Barbara Nemesure.

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Nemesure, B., Jiao, X., He, Q. et al. A genome-wide scan for primary open-angle glaucoma (POAG): the Barbados Family Study of Open-Angle Glaucoma. Hum Genet 112, 600–609 (2003). https://doi.org/10.1007/s00439-003-0910-z

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  • DOI: https://doi.org/10.1007/s00439-003-0910-z

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