一项关于43的国际研究,000 people has significantly expanded the number of genetic factors known to play a role in 年龄相关性黄斑变性（AMD）, a leading cause of 视力丧失 among people age 50 and older. The study was supported by the National Eye Institute (NEI), part of the National Institutes of Health, and involved an international team of scientists including 研究ers from the 犹他大学的John A. 莫兰眼科中心. The findings may help improve our understanding of the biological processes that lead to AMD and identify new therapeutic targets for potential drug development.
AMD is a progressive disease that causes the death of the retinal photoreceptors, the light-sensitive cells at the back of the eye. The most severe damage occurs in the macula, a small area of the retina that is needed for sharp, 中央视觉是阅读所必需的, 驾驶和其他日常工作. There are currently no Food and Drug Administration-approved treatments for the more common form of advanced AMD, called geographic atrophy or "dry" AMD. While therapies for the other advanced form, 新生血管性或“湿性”AMD, can successfully halt the growth of abnormal, 眼睛血管渗漏, the therapies do not cure the condition, 它们也不是对所有人都适用.
AMD is caused by a combination of genetic, environmental and lifestyle risk factors. 例如, 吸烟会增加患AMD的风险, 同时吃绿叶蔬菜和鱼, 比如三文鱼, 大比目鱼, 和金枪鱼, 可以降低风险. 到目前为止, 研究ers had identified 21 regions of the genome—called loci—that influence the risk of AMD. 这项新研究发表在 自然遗传学这样，基因座的数量就增加到了34个.
"These exciting findings provide the basis for functional studies which will speed the development of targeted drug therapies,” 玛格丽特·迪安吉利斯博士, a senior author of the study and associate professor of Ophthalmology and Visual Sciences at the University of Utah.
The International AMD Genomics Consortium, 其中包括全球26个中心, collected and analyzed the genetic data from 43,566 people of predominantly European ancestry to systematically identify common and rare variations in genetic coding—called variants—associated with AMD. Common variants generally have an indirect association with a disease. 罕见变异, 相比之下, are more likely to alter protein expression or function and therefore have a direct or causal association with a disease. 罕见变异 were defined as those found in less than 1 percent of the study population.
The study included about 23,000 participants with AMD and 20,000 without it. The 研究ers analyzed DNA samples from both groups, 研究大部分基因组, but also focusing in on distinct loci already known or suspected to be associated with AMD. 下一个, they compared the participants' DNA to a reference dataset called the 1000 Genomes project, yielding more than 12 million genetic variants of potential interest. 最后, they went back to the participants' DNA samples, 看看所有的1200万种变体, to see if any were found more or less often in people with AMD than those without it.
The 研究ers have now discovered a total of 52 genetic variants that are associated with AMD. These variants are located among 34 loci, 16 of which had not been previously associated with AMD.
The study findings also bolster associations between AMD and two genes, CFH和TIMP3, which had each previously been linked to AMD. CFH was the very first disease-linked gene to be found through a genome-wide association study. TIMP3 had earlier been linked to Sorsby's fundus dystrophy, a rare disease that is similar to AMD clinically, but that tends to affect people before the age of 45.
For the first time the 研究ers also identified a variant specific to the neovascular form of AMD, which may point to reasons why therapy for this form of AMD is effective for some people but not everyone.
另外, 10 of the variants point to genes involved in maintaining the extracellular matrix, the nonliving material amongst cells that provides structural support and nutrients. 研究ers have theorized that abnormalities of the extracellular matrix occur in people with a subtype of AMD that develops without early-stage signs, or that quickly worsens before such signs are detected. 如果得到证实, a connection between AMD and these extracellular matrix genes may allow for predictive genetic tests and more effective therapies for people with this type of AMD.
其他来自 犹他大学的John A. 莫兰眼科中心 include Debra Schaumberg, PhD, Margaux Crabtree Morrison, and Denise Morgan.
The study was funded in part by NEI Intramural 研究 Program and by NEI grants: EY023164, EY012118, EY022310, T32-EY023194, P30-EY005722, EY0022005, EY016862, EY022310. The study also was supported by NIH grants from the National Human Genome 研究 Institute (HG006513, HG007022, 1 u01hg006389), the National Institute on Aging (AG019085), and the National Center for Advancing Translational Sciences (UL1TR000427).
引用:
The International AMD Genomics Consortium, "Insights into Rare and Common Genetic Variation from a Large Study of Age-Related Macular Degeneration," 自然遗传学， 2015年12月21日上线. DOI: 10.1038/ng.3448