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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados
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Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados

机译:巴巴多斯的非洲加勒比海地区人口2号染色体上的常见变异和原发性开角型青光眼的风险

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摘要

Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Although a number of genetic loci have shown association or genetic linkage to monogenic forms of POAG, the identified genes and loci do not appear to have a major role in the common POAG phenotype. We seek to identify genetic loci that appear to be major risk factors for POAG in the Afro-Caribbean population of Barbados, West Indies. We performed linkage analyses in 146 multiplex families ascertained through the Barbados Family Study of Glaucoma (BFSG) and identified a strong linkage signal on chromosome 2p (logarithm of odds score = 6.64 at 0 = 0 with marker D2S2156). We subsequently performed case-control analyses using unrelated affected individuals and unaffected controls. A set of SNPs on chromosome 2p was evaluated in two independent groups of BFSG participants, a discovery group (130 POAG cases, 65 controls) and a replication group (122 POAG cases, 65 controls), and a strong association was identified with POAG and rs12994401 in both groups (P < 3.34 E-09 and P < 1.21E-12, respectively). The associated SNPs form a common disease haplo-type. In summary, we have identified a locus with a major impact on susceptibility to the common POAG phenotype in an Afro-Caribbean population in Barbados. Our approach illustrates the merit of using an isolated population enriched with common disease variants as an efficient method to identify genetic underpinning of POAG.
机译:原发性开角型青光眼(POAG)是全球失明的第二大主要原因。尽管许多遗传基因座已经显示出与单基因形式的POAG相关或遗传连锁,但是鉴定出的基因和基因座似乎在普通POAG表型中没有主要作用。我们力求确定似乎是西印度群岛巴巴多斯的非洲加勒比海人口中POAG的主要危险因素的遗传基因座。我们在通过巴巴多斯青光眼家族研究(BFSG)确定的146个多重家族中进行了连锁分析,并在2p染色体上发现了强连锁信号(0 = 0时,D2S2156标记的对数得分对数= 6.64)。随后,我们使用不相关的受影响个体和未受影响的对照进行了病例对照分析。在BFSG参与者的两个独立组(一个发现组(130个POAG病例,65个对照)和一个复制组(122个POAG病例,65个对照))中评估了2p号染色体上的一组SNP,并确定了与POAG和两组均为rs12994401(分别为P <3.34 E-09和P <1.21E-12)。相关的SNP形成常见的疾病单倍型。总而言之,我们确定了一个对巴巴多斯的非洲加勒比海人群中常见POAG表型易感性的位点。我们的方法说明了使用富含常见疾病变体的隔离种群作为鉴定POAG遗传基础的有效方法的优点。

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  • 作者单位

    Ophthalmic Genetics and Visual Function Branch, National Eye Institute, and Barbados Family Study Group, National Institutes of Health, Bethesda, MD 20892;

    lnstitute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838 Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132 Center for Human Biology and Genetics, Sichuan Provincial People's Hospital, Sichuan 610072, China;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838 Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132 Department of Ophthalmology,School of Medicine, Qingdao University, Qingdao 266021, China;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838 Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132 Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China;

    Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838 Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838 Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132;

    Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132;

    Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84132;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838;

    Department of Preventive Medicine, School of Medicine, and Barbados Family Study Group, Stony Brook University, Stony Brook, NY 11794;

    Ministry of Health, Barbados, West Indies, Chronic Disease Research Centre, Tropical Medicine Research Institute, and Barbados Family Study Group, University of the West Indies, Barbados, West Indies;

    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06520;

    Department of Preventive Medicine, School of Medicine, and Barbados Family Study Group, Stony Brook University, Stony Brook, NY 11794;

    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84132;

    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06520;

    Ophthalmic Genetics and Visual Function Branch, National Eye Institute, and Barbados Family Study Group, National Institutes of Health, Bethesda, MD 20892;

    Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093-0838 Moran Eye Center , University of Utah School of Medicine, Salt Lake City, UT 84132 Department of Ophthalmology and Ophthalmic Laboratories, West China Hospital, Sichuan 610041, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    association study; linkage analysis; SNP; eye; intraocular pressure;

    机译:关联研究;连锁分析;SNP;眼睛;眼压;

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