网状拟麻和拟麻的遗传差异：全基因组关联研究。

IF 4.1 1区医学 Q1 OPHTHALMOLOGY

American Journal of Ophthalmology Pub Date : 2025-03-09 DOI:10.1016/j.ajo.2025.03.007

Roy Schwartz , Alasdair N. Warwick , Anthony P. Khawaja , Robert Luben , Hagar Khalid , Sumita Phatak , Mahima Jhingan , Coen de Vente , Philippe Valmaggia , Sandra Liakopoulos , Abraham Olvera-Barrios , Clara I. Sánchez , Catherine Egan , Roberto Bonelli , Adnan Tufail

{"title":"网状拟麻和拟麻的遗传差异：全基因组关联研究。","authors":"Roy Schwartz , Alasdair N. Warwick , Anthony P. Khawaja , Robert Luben , Hagar Khalid , Sumita Phatak , Mahima Jhingan , Coen de Vente , Philippe Valmaggia , Sandra Liakopoulos , Abraham Olvera-Barrios , Clara I. Sánchez , Catherine Egan , Roberto Bonelli , Adnan Tufail","doi":"10.1016/j.ajo.2025.03.007","DOIUrl":null,"url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To identify genetic determinants specific to reticular pseudodrusen (RPD) compared with drusen.</div></div><div><h3>DESIGN</h3><div>Genome-wide association study (GWAS)</div></div><div><h3>SUBJECTS</h3><div>Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort.</div></div><div><h3>METHODS</h3><div>Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort, were included. A deep learning framework analyzed 169,370 optical coherence tomography (OCT) volumes to identify cases and controls within the UKBB. Five retina specialists validated the cohorts using OCT and color fundus photographs. Several GWAS were undertaken utilizing the quantity and presence of RPD and drusen. Genome-wide significance was defined as <em>P</em> < 5e-8.</div></div><div><h3>MAIN OUTCOMES MEASURES</h3><div>Genetic associations were examined with the number of RPD and drusen within ‘pure’ cases, where only RPD or drusen were present in either eye. A candidate approach assessed 46 previously known AMD loci. Secondary GWAS were conducted for number of RPD and drusen in mixed cases, and binary case-control analyses for pure RPD and pure drusen.</div></div><div><h3>RESULTS</h3><div>The study included 1787 participants: 1037 controls, 361 pure drusen, 66 pure RPD, and 323 mixed cases. The primary pure RPD GWAS identified four genome-wide significant loci: rs11200630 near <em>ARMS2</em>-<em>HTRA1</em> (<em>P</em> = 1.9e-09), rs79641866 at <em>PARD3B</em> (<em>P</em> = 1.3e-08), rs143184903 near <em>ITPR1</em> (<em>P</em> = 8.1e-09), and rs76377757 near <em>SLN</em> (<em>P</em> = 4.3e-08). The latter three are uncommon variants (minor allele frequency <5%). A significant association at the <em>CFH</em> locus was also observed using a candidate approach (<em>P</em> = 1.8e-04). For pure drusen, two loci reached genome-wide significance: rs10801555 at <em>CFH</em> (<em>P</em> = 6.0e-33) and rs61871744 at <em>ARMS2</em>-<em>HTRA1</em> (<em>P</em> = 4.2e-20).</div></div><div><h3>CONCLUSIONS</h3><div>The study highlights a clear association between the <em>ARMS2-HTRA1</em> locus and higher RPD load. Although the <em>CFH</em> locus association did not achieve genome-wide significance, a suggestive link was observed. Three novel associations unique to RPD were identified, albeit for uncommon genetic variants. Further studies with larger sample sizes are needed to explore these findings.</div></div>","PeriodicalId":7568,"journal":{"name":"American Journal of Ophthalmology","volume":"274 ","pages":"Pages 286-295"},"PeriodicalIF":4.1000,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic Distinctions Between Reticular Pseudodrusen and Drusen: A Genome-Wide Association Study\",\"authors\":\"Roy Schwartz , Alasdair N. Warwick , Anthony P. Khawaja , Robert Luben , Hagar Khalid , Sumita Phatak , Mahima Jhingan , Coen de Vente , Philippe Valmaggia , Sandra Liakopoulos , Abraham Olvera-Barrios , Clara I. Sánchez , Catherine Egan , Roberto Bonelli , Adnan Tufail\",\"doi\":\"10.1016/j.ajo.2025.03.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>OBJECTIVE</h3><div>To identify genetic determinants specific to reticular pseudodrusen (RPD) compared with drusen.</div></div><div><h3>DESIGN</h3><div>Genome-wide association study (GWAS)</div></div><div><h3>SUBJECTS</h3><div>Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort.</div></div><div><h3>METHODS</h3><div>Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort, were included. A deep learning framework analyzed 169,370 optical coherence tomography (OCT) volumes to identify cases and controls within the UKBB. Five retina specialists validated the cohorts using OCT and color fundus photographs. Several GWAS were undertaken utilizing the quantity and presence of RPD and drusen. Genome-wide significance was defined as <em>P</em> < 5e-8.</div></div><div><h3>MAIN OUTCOMES MEASURES</h3><div>Genetic associations were examined with the number of RPD and drusen within ‘pure’ cases, where only RPD or drusen were present in either eye. A candidate approach assessed 46 previously known AMD loci. Secondary GWAS were conducted for number of RPD and drusen in mixed cases, and binary case-control analyses for pure RPD and pure drusen.</div></div><div><h3>RESULTS</h3><div>The study included 1787 participants: 1037 controls, 361 pure drusen, 66 pure RPD, and 323 mixed cases. The primary pure RPD GWAS identified four genome-wide significant loci: rs11200630 near <em>ARMS2</em>-<em>HTRA1</em> (<em>P</em> = 1.9e-09), rs79641866 at <em>PARD3B</em> (<em>P</em> = 1.3e-08), rs143184903 near <em>ITPR1</em> (<em>P</em> = 8.1e-09), and rs76377757 near <em>SLN</em> (<em>P</em> = 4.3e-08). The latter three are uncommon variants (minor allele frequency <5%). A significant association at the <em>CFH</em> locus was also observed using a candidate approach (<em>P</em> = 1.8e-04). For pure drusen, two loci reached genome-wide significance: rs10801555 at <em>CFH</em> (<em>P</em> = 6.0e-33) and rs61871744 at <em>ARMS2</em>-<em>HTRA1</em> (<em>P</em> = 4.2e-20).</div></div><div><h3>CONCLUSIONS</h3><div>The study highlights a clear association between the <em>ARMS2-HTRA1</em> locus and higher RPD load. Although the <em>CFH</em> locus association did not achieve genome-wide significance, a suggestive link was observed. Three novel associations unique to RPD were identified, albeit for uncommon genetic variants. Further studies with larger sample sizes are needed to explore these findings.</div></div>\",\"PeriodicalId\":7568,\"journal\":{\"name\":\"American Journal of Ophthalmology\",\"volume\":\"274 \",\"pages\":\"Pages 286-295\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-03-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0002939425001199\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0002939425001199","RegionNum":1,"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

摘要

目的：鉴别网状假性丘疹（RPD）与丘疹的遗传决定因素。设计：全基因组关联研究（GWAS）受试者：来自英国生物银行（UKBB）的RPD、dren和对照患者，这是一个大型、多地点、基于社区的队列研究。方法：深度学习框架分析了169,370个光学相干断层扫描（OCT）卷，以识别UKBB中的病例和对照。五名视网膜专家使用OCT和彩色眼底照片验证了这些队列。利用RPD和dren的数量和存在进行了几次GWAS。全基因组显著性定义为：主要结果测量：在“纯”病例中，通过RPD和drusen的数量检查遗传关联，其中只有RPD或drusen存在于任何一只眼睛。一种候选方法评估了46个先前已知的AMD位点。对混合病例的RPD数和dren数进行二次GWAS，对纯RPD和纯dren进行二元病例对照分析。结果：该研究包括1787名参与者：1037名对照，361名纯dren， 66名纯RPD和323名混合病例。初级纯RPD GWAS鉴定出4个全基因组显著位点：ARMS2-HTRA1附近的rs11200630 (p=1.9e-09)， PARD3B附近的rs79641866 (p=1.3e-08)， ITPR1附近的rs143184903 (p=8.1e-09)， SLN附近的rs76377757 （p=4.3e-08）。结论：该研究强调了ARMS2-HTRA1位点与较高的RPD负荷之间的明确关联。虽然CFH位点的关联没有达到全基因组的意义，但我们观察到一种暗示性的联系。尽管存在不常见的遗传变异，但仍发现了RPD特有的三种新关联。需要更大样本量的进一步研究来探索这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Genetic Distinctions Between Reticular Pseudodrusen and Drusen: A Genome-Wide Association Study

OBJECTIVE

To identify genetic determinants specific to reticular pseudodrusen (RPD) compared with drusen.

DESIGN

Genome-wide association study (GWAS)

SUBJECTS

Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort.

METHODS

Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort, were included. A deep learning framework analyzed 169,370 optical coherence tomography (OCT) volumes to identify cases and controls within the UKBB. Five retina specialists validated the cohorts using OCT and color fundus photographs. Several GWAS were undertaken utilizing the quantity and presence of RPD and drusen. Genome-wide significance was defined as P < 5e-8.

MAIN OUTCOMES MEASURES

Genetic associations were examined with the number of RPD and drusen within ‘pure’ cases, where only RPD or drusen were present in either eye. A candidate approach assessed 46 previously known AMD loci. Secondary GWAS were conducted for number of RPD and drusen in mixed cases, and binary case-control analyses for pure RPD and pure drusen.

RESULTS

The study included 1787 participants: 1037 controls, 361 pure drusen, 66 pure RPD, and 323 mixed cases. The primary pure RPD GWAS identified four genome-wide significant loci: rs11200630 near ARMS2-HTRA1 (P = 1.9e-09), rs79641866 at PARD3B (P = 1.3e-08), rs143184903 near ITPR1 (P = 8.1e-09), and rs76377757 near SLN (P = 4.3e-08). The latter three are uncommon variants (minor allele frequency <5%). A significant association at the CFH locus was also observed using a candidate approach (P = 1.8e-04). For pure drusen, two loci reached genome-wide significance: rs10801555 at CFH (P = 6.0e-33) and rs61871744 at ARMS2-HTRA1 (P = 4.2e-20).

CONCLUSIONS

The study highlights a clear association between the ARMS2-HTRA1 locus and higher RPD load. Although the CFH locus association did not achieve genome-wide significance, a suggestive link was observed. Three novel associations unique to RPD were identified, albeit for uncommon genetic variants. Further studies with larger sample sizes are needed to explore these findings.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

American Journal of Ophthalmology 医学-眼科学

CiteScore

9.20

自引率

7.10%

发文量

406

审稿时长

36 days

期刊介绍： The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations, and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented online at www.AJO.com and on ScienceDirect. The American Journal of Ophthalmology publishes Full-Length Articles, Perspectives, Editorials, Correspondences, Books Reports and Announcements. Brief Reports and Case Reports are no longer published. We recommend submitting Brief Reports and Case Reports to our companion publication, the American Journal of Ophthalmology Case Reports. Manuscripts are accepted with the understanding that they have not been and will not be published elsewhere substantially in any format, and that there are no ethical problems with the content or data collection. Authors may be requested to produce the data upon which the manuscript is based and to answer expeditiously any questions about the manuscript or its authors.