Gene-environment-wide interaction studies of ocular refraction

描述（由申请人提供）：屈光不正（近视和远视）是最普遍的人类眼部疾病。到2020年，全世界三分之一的人口超过25亿人将受到近视的影响。据估计，未矫正屈光不正造成的全球经济生产力损失为2680亿美元。因此，屈光不正是一个重要的公共卫生问题，特别是在东亚地区，近视已经达到“流行病”的比例。 屈光不正是一种复杂的性状，遗传和环境/行为因素都被认为起着重要作用。本项目的目的是在全基因组关联研究的背景下研究基因-环境相互作用对眼屈光的影响。这项研究将利用在美国、德国和新加坡进行的基因组研究的6个大型数据集。我们的具体目标是：1）在屈光不正的基因-环境相互作用研究中发现与环境因素相互作用的遗传多态性; 2）鉴定环境因素介导人类屈光不正发展的生物学途径或基因组。这项研究的最终目标是更好地了解眼睛屈光发育的复杂生物学，并确定与屈光不正中的环境因素（通过暴露于高视觉需求的代理来测量，如教育和阅读）相互作用的特定基因。 这项研究是K 08指导临床科学家研究职业发展奖的一部分。赠款期间的培训将侧重于培养设计、管理、分析和解释大规模基因-环境研究所需的技能。Wojciechowski博士的长期职业生涯将致力于将大型基因组研究提供的大量数据转化为临床有用，可理解和实用的信息。这些信息最终将使科学家、临床医生、公共卫生从业人员、政策制定者以及最重要的是广大公众受益。

DESCRIPTION (provided by applicant): Refractive errors (myopia and hyperopia) are the most widespread human eye disorders. By the year 2020, one third of the world's population-over 2.5 billion people-will be affected by myopia alone. The global economic productivity loss from uncorrected refractive errors has been estimated to be $268 billion. Hence, refractive errors are a significant Public Health problem, especially in regions of East Asia where myopia has reached �epidemic� proportions. Refractive errors are complex traits, in which both inherited genetic and environmental/behavioral factors are thought to play significant roles. The objective of this project is to study the effects of gene-environment interactions on ocular refraction within the context of whole-genome association studies. The proposed research will make use of 6 large datasets from genomic studies conducted in the United States, Germany, and Singapore. Our specific aims are to: 1) discover of genetic polymorphisms which interact with environmental factors in gene-environment-wide interaction studies of refractive error; and 2) identify biological pathways or gene-sets through which environmental factors mediate refractive error development in humans. The ultimate goals of the research are to better understand the complex biology of ocular refractive development, and identify specific genes which interact with environmental factors (as measured by proxies of exposure to high visual demand, such as education and reading) in refractive error. The proposed research is part of a K08 Mentored Clinical Scientist Research Career Development Award. Training in the grant period will focus on developing skills necessary in the design, management, analysis and interpretation of large-scale gene-environment-wide studies. Dr. Wojciechowski's long-term career will be devoted to translating the vast data provided by large genomic studies into clinically useful, comprehensible, and practical information. This information will ultimately benefit scientists, clinicians, Public Health practitioners, policy makers and, most importantly, the public at large.