Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy.

IF 5 2区 医学 Q1 OPHTHALMOLOGY
Rajya L Gurung, Charvi Nangia, Tengda Cai, Liesel M FitzGerald, Bennet J McComish, Ebony Liu, Georgia Kaidonis, Bronwyn Ridge, Alex W Hewitt, Brendan Vote, Nitin Verma, Jamie E Craig, Colin N A Palmer, Kathryn P Burdon, Weihua Meng
{"title":"Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy.","authors":"Rajya L Gurung, Charvi Nangia, Tengda Cai, Liesel M FitzGerald, Bennet J McComish, Ebony Liu, Georgia Kaidonis, Bronwyn Ridge, Alex W Hewitt, Brendan Vote, Nitin Verma, Jamie E Craig, Colin N A Palmer, Kathryn P Burdon, Weihua Meng","doi":"10.1167/iovs.66.3.55","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis. The Australian cohort comprised 551 cases of DME and 599 controls recruited from the states of South Australia and Tasmania. The Scottish cohort comprised 1951 cases of diabetic maculopathy and 6541 controls from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS). Genotyping, imputation, and association analysis using logistic regression were conducted in each cohort, before combining summary statistics in a meta-analysis using the GWAMA package.</p><p><strong>Results: </strong>A locus on chromosome 7 reached genome-wide significance in GoDARTS but showed the opposite direction of effect in the Australian cohort. The meta-analysis identified two suggestive associations (P < 5 × 10-6) for diabetic maculopathy risk with similar effect direction; one at chromosome 1 close to the RNU5E-1 gene and one at chromosome 13 upstream of the ERICH6B gene. The two loci were evaluated in silico for potential functional links to diabetic maculopathy. Both are located in regulatory regions and have annotations indicating regulatory functions. They are also expression quantitative trait locus (eQTLs) for genes plausibly involved in diabetic maculopathy pathogenesis, with links to folate metabolism and the regulation of VEGF.</p><p><strong>Conclusions: </strong>The study suggests several promising SNPs and genes related to diabetic maculopathy risk. Despite being the largest genetic study of diabetic maculopathy to date, larger, homogeneous cohorts will be required to identify robust genetic risk loci for the disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"55"},"PeriodicalIF":5.0000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951052/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Investigative ophthalmology & visual science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1167/iovs.66.3.55","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Diabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.

Methods: We conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis. The Australian cohort comprised 551 cases of DME and 599 controls recruited from the states of South Australia and Tasmania. The Scottish cohort comprised 1951 cases of diabetic maculopathy and 6541 controls from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS). Genotyping, imputation, and association analysis using logistic regression were conducted in each cohort, before combining summary statistics in a meta-analysis using the GWAMA package.

Results: A locus on chromosome 7 reached genome-wide significance in GoDARTS but showed the opposite direction of effect in the Australian cohort. The meta-analysis identified two suggestive associations (P < 5 × 10-6) for diabetic maculopathy risk with similar effect direction; one at chromosome 1 close to the RNU5E-1 gene and one at chromosome 13 upstream of the ERICH6B gene. The two loci were evaluated in silico for potential functional links to diabetic maculopathy. Both are located in regulatory regions and have annotations indicating regulatory functions. They are also expression quantitative trait locus (eQTLs) for genes plausibly involved in diabetic maculopathy pathogenesis, with links to folate metabolism and the regulation of VEGF.

Conclusions: The study suggests several promising SNPs and genes related to diabetic maculopathy risk. Despite being the largest genetic study of diabetic maculopathy to date, larger, homogeneous cohorts will be required to identify robust genetic risk loci for the disease.

确定与糖尿病黄斑病变相关的遗传变异的全基因组关联研究。
目的:糖尿病性黄斑病变(包括糖尿病性黄斑水肿[DME])是糖尿病患者视力丧失的主要原因。我们的目的是确定糖尿病黄斑病变的遗传决定因素。方法:我们在两个队列中进行了全基因组关联研究(GWAS),并进行了荟萃分析。澳大利亚队列包括从南澳大利亚州和塔斯马尼亚州招募的551例二甲醚病例和599例对照。苏格兰队列包括1951例糖尿病黄斑病变和6541例对照,来自苏格兰泰赛德研究糖尿病遗传学审计和研究(GoDARTS)。在每个队列中使用逻辑回归进行基因分型、归因和关联分析,然后使用GWAMA软件包在荟萃分析中结合汇总统计。结果:7号染色体上的一个位点在godart中达到全基因组意义,但在澳大利亚队列中显示相反的方向。荟萃分析发现糖尿病黄斑病变风险有两种相关性(P < 5 × 10-6),作用方向相似;一个位于靠近RNU5E-1基因的1号染色体上,一个位于ERICH6B基因上游的13号染色体上。这两个基因座被计算机评估与糖尿病黄斑病变的潜在功能联系。两者都位于调控区域,并具有指示调控功能的注释。它们也是表达数量性状位点(eQTLs)的基因,可能与糖尿病黄斑病变的发病机制有关,与叶酸代谢和VEGF的调节有关。结论:该研究提示了几个与糖尿病黄斑病变风险相关的有希望的snp和基因。尽管是迄今为止最大的糖尿病黄斑病变遗传研究,但需要更大的同质队列来确定该疾病的强大遗传风险位点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信