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：
8726405
负责人：
Janey L Wiggs
金额：
$ 68万
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/8726405
关键词：
Affect 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 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 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 risk variant screening

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（由申请人提供）：去角质综合征（ES）是一种常见的疾病，其特征是在整个眼前部分中大分子的异质混合物沉积。导致该材料积聚在ES中的因素仍然未知。 ES是一个公共卫生问题，因为它是高张力开开角糖瘤，成熟的白内障形成以及白内障手术中并发症风险增加的危险因素。先前的研究表明，去角质综合征和相关的青光眼在遗传上是复杂的，而一个基因LOXL1已被鉴定为主要的遗传危险因素。在多达98％的受影响的患者中发现LOXL1基因变体。但是，这些相同的变体也有多达80％的未受影响的个体存在，这表明其他遗传和/或环境因素对于疾病的发展是必需的。进一步的证据表明，LOXL1是必要的，但对于该疾病不足，这是我们对LOXL1 NULL小鼠的初步研究，该研究确定了某些疾病的某些表型特征。为了确定导致去角质综合征和去角色青光眼的其他遗传和环境因素，我们形成了一个合作联盟，贡献了2300多种剥落病例和2300个控制。整个基因组基因分型已经在650例和2250例控制中完成，超过1000例具有详细的环境暴露。我们将执行一个单阶段的GWA，以识别与去角质综合征相关的其他遗传标记，还将研究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，北纬地区的住所影响。新发现的遗传和环境风险因素将分析基因环境和基因 - 基因相互作用。