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Genetic and Environmental Risk Factors for Exfoliation Syndrome and Glaucoma

剥脱性综合征和青光眼的遗传和环境风险因素

基本信息

批准号：
8323486
负责人：
Janey L Wiggs
金额：
$ 72.21万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8323486
关键词：
Affect Alleles Anterior eyeball segment structure Aqueous Humor Caffeine Case-Control Studies Cataract Cataract Extraction Climate Clinic Complex Consumption Data Deposition Development Diet Dietary Factors Disease Ear Environment Environmental Exposure Environmental Risk Factor Evaluation Exfoliation Syndrome Eye Folate Frequencies Genes Genetic Genetic Markers Genetic Risk Genetic Variation Genome Genomics Genotype German population Glaucoma Goals Health Health Professional Homocysteine Homocystine Individual Intake Knockout Mice Life Massachusetts Meta-Analysis Morbidity - disease rate Nurses&apos Health Study Open-Angle Glaucoma Pathogenesis Patients Physicians Plasma Population Study Prevention strategy Public Health Recording of previous events Regulation Relative Risks Research Resources Risk Risk Factors Sampling Screening procedure Single Nucleotide Polymorphism Smoking Staging Testing Translating United States Universities Variant Vitamin B 12 Vitamin B6 Woman base case control disorder risk follow-up gene environment interaction gene interaction genetic epidemiology genetic risk factor genetic variant genome wide association study genome-wide hazard macromolecule novel novel strategies population based residence

项目摘要

DESCRIPTION (provided by applicant): Exfoliation syndrome (ES) is a common condition characterized by deposition of a heterogeneous mix of macromolecules throughout the anterior segment of the eye. The factors that cause this material to accumulate in ES remain unknown. ES is a public health problem, because it is a risk factor for high-tension open-angle glaucoma, pre-mature cataract formation, and increased risk of complications during cataract surgery. Previous studies suggest that exfoliation syndrome and the related glaucoma are genetically complex, and one gene, LOXL1, has been identified as a major genetic risk factor. LOXL1 gene variants are found in up to 98% of affected patients; however, these same variants are also present in up to 80% of unaffected individuals, indicating that additional genetic and/or environmental factors are necessary for disease development. Further evidence that LOXL1 is necessary but not sufficient for the disease comes from our preliminary studies of the LOXL1 null mouse that identified some, but not all the phenotypic features of the condition. To identify additional genetic and environmental factors contributing to exfoliation syndrome and exfoliation glaucoma, we have formed a collaborative consortium contributing over 2300 exfoliation cases and 2300 controls. Whole genome genotyping has already been completed in 650 cases and 2250 controls, and over 1000 cases have detailed environmental exposures. We will perform a single stage GWAS to identify additional genetic markers associated with exfoliation syndrome, and will also investigate associations between ES and environmental exposures including factors that influence homocysteine levels the effect of residence in northern latitude. Newly discovered genetic and environmental risk factors will be analyzed for gene- environment and gene-gene interactions.

描述(申请人提供)：剥脱综合征(ES)是一种常见的情况，其特征是大分子的不同混合物沉积在整个眼前段。导致这种物质在ES中积累的因素尚不清楚。ES是一个公共卫生问题，因为它是高眼压性开角型青光眼、早熟白内障形成的危险因素，并增加了白内障手术中并发症的风险。以往的研究表明，剥脱综合征和相关的青光眼在遗传上是复杂的，其中一个基因LOXL1已被确定为主要的遗传风险因素。LOXL1基因变异在高达98%的受影响患者中被发现；然而，这些相同的变异也存在于高达80%的未受影响的个体中，这表明额外的遗传和/或环境因素对于疾病的发展是必要的。进一步的证据表明LOXL1对于疾病是必要的，但不是充分的，来自我们对LOXL1缺失小鼠的初步研究，发现了这种疾病的一些但不是全部的表型特征。为了确定导致剥脱综合征和剥脱性青光眼的其他遗传和环境因素，我们组成了一个协作性联盟，提供了2300多例剥脱病例和2300例对照。650例患者和2250名对照已经完成了全基因组基因分型，超过1000例患者有详细的环境暴露。我们将进行单一阶段的GWAS，以确定与剥脱综合征相关的其他遗传标记，并将调查ES与环境暴露之间的关联，包括影响同型半胱氨酸水平的因素，以及居住在北纬的影响。将对新发现的遗传和环境风险因素进行基因-环境和基因-基因相互作用的分析。