Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-05-06 DOI:10.1016/j.xops.2025.100821

Nobuo Fuse MD, PhD , Hayato Anzawa PhD , Miyuki Sakurai PhD , Ikuko N. Motoike PhD , Satoshi Nagaie PhD , Tomohiro Nakamura PhD , Akiko Miyazawa MD, PhD , Eiichi N. Kodama MD, PhD , Masatsugu Orui MD, PhD , Yohei Hamanaka MD, PhD , Tomoko Kobayashi MD, PhD , Akira Uruno MD, PhD , Makiko Taira MD, PhD , Ritsuko Shimizu MD, PhD , Naoki Nakaya PhD , Mami Ishikuro PhD , Taku Obara PhD , Fuji Nagami PhD , Soichi Ogishima PhD , Fumiki Katsuoka PhD , Masayuki Yamamoto MD, PhD

{"title":"Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study","authors":"Nobuo Fuse MD, PhD , Hayato Anzawa PhD , Miyuki Sakurai PhD , Ikuko N. Motoike PhD , Satoshi Nagaie PhD , Tomohiro Nakamura PhD , Akiko Miyazawa MD, PhD , Eiichi N. Kodama MD, PhD , Masatsugu Orui MD, PhD , Yohei Hamanaka MD, PhD , Tomoko Kobayashi MD, PhD , Akira Uruno MD, PhD , Makiko Taira MD, PhD , Ritsuko Shimizu MD, PhD , Naoki Nakaya PhD , Mami Ishikuro PhD , Taku Obara PhD , Fuji Nagami PhD , Soichi Ogishima PhD , Fumiki Katsuoka PhD , Masayuki Yamamoto MD, PhD","doi":"10.1016/j.xops.2025.100821","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>This study was conducted to elucidate the distribution and determinants of ocular biometric parameters and to assess the association between intraocular pressure (IOP) and single nucleotide polymorphisms (SNPs) in the Japanese population–based genome cohort studies.</div></div><div><h3>Design</h3><div>Cross-sectional analysis involving genome-wide association studies (GWASs).</div></div><div><h3>Participants</h3><div>In total, 22 150 participants aged >18 years from the population cohort (Community-Based Cohort [CommCohort]) and 11 302 participants from the Birth and Three-Generation (BirThree) Cohort of the Tohoku Medical Megabank Organization Eye Study were examined.</div></div><div><h3>Methods</h3><div>Participant underwent interviews, ophthalmic and physiological examinations, laboratory tests, and microarray analyses. Genome-wide association studies were conducted in the CommCohort (discovery stage) and the BirThree Cohort (replication stage), followed by a meta-analysis. Associations of SNPs and IOP were evaluated using a genome-wide significance threshold (5 × 10<sup>−</sup><sup>8</sup>).</div></div><div><h3>Main Outcome Measures</h3><div>Association of SNPs with IOP and distributions of IOP by sex and age.</div></div><div><h3>Results</h3><div>In the discovery stage, the mean IOP of the right and left eye was 13.95 and 14.02 mmHg, respectively. In the replication stage, the corresponding values were 14.32 and 14.27 mmHg, respectively. A significant age-related reduction in IOP was observed in both stages (<em>P</em> < 0.001). Genome-wide association studies identified 573 and 2 genome-wide significant SNPs in the discovery and replication stages, respectively. Meta-analysis revealed 1601 significant SNPs across 21 loci on 11 chromosomes (Chrs). Of these loci, 17 were previously known to be associated with IOP or glaucoma, while four—septin-8 (<em>SEPT8</em>; Chr5), aldehyde dehydrogenase 2 (<em>ALDH2</em>; Chr12), collagen type VI alpha 2 chain (<em>COL6A2</em>; Chr21), and Wnt family member 7B (<em>WNT7B</em>; Chr22)—were newly identified.</div></div><div><h3>Conclusions</h3><div>This large-scale GWAS in a Japanese population identified 21 loci associated with IOP, including 4 novel loci. The findings highlight both genetic similarities and population-specific variations in SNPs influencing IOP and provide valuable insights to enhance eye health care, including glaucoma management.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 5","pages":"Article 100821"},"PeriodicalIF":3.2000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmology science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666914525001198","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose

This study was conducted to elucidate the distribution and determinants of ocular biometric parameters and to assess the association between intraocular pressure (IOP) and single nucleotide polymorphisms (SNPs) in the Japanese population–based genome cohort studies.

Design

Cross-sectional analysis involving genome-wide association studies (GWASs).

Participants

In total, 22 150 participants aged >18 years from the population cohort (Community-Based Cohort [CommCohort]) and 11 302 participants from the Birth and Three-Generation (BirThree) Cohort of the Tohoku Medical Megabank Organization Eye Study were examined.

Methods

Participant underwent interviews, ophthalmic and physiological examinations, laboratory tests, and microarray analyses. Genome-wide association studies were conducted in the CommCohort (discovery stage) and the BirThree Cohort (replication stage), followed by a meta-analysis. Associations of SNPs and IOP were evaluated using a genome-wide significance threshold (5 × 10⁻⁸).

Main Outcome Measures

Association of SNPs with IOP and distributions of IOP by sex and age.

Results

In the discovery stage, the mean IOP of the right and left eye was 13.95 and 14.02 mmHg, respectively. In the replication stage, the corresponding values were 14.32 and 14.27 mmHg, respectively. A significant age-related reduction in IOP was observed in both stages (P < 0.001). Genome-wide association studies identified 573 and 2 genome-wide significant SNPs in the discovery and replication stages, respectively. Meta-analysis revealed 1601 significant SNPs across 21 loci on 11 chromosomes (Chrs). Of these loci, 17 were previously known to be associated with IOP or glaucoma, while four—septin-8 (SEPT8; Chr5), aldehyde dehydrogenase 2 (ALDH2; Chr12), collagen type VI alpha 2 chain (COL6A2; Chr21), and Wnt family member 7B (WNT7B; Chr22)—were newly identified.

Conclusions

This large-scale GWAS in a Japanese population identified 21 loci associated with IOP, including 4 novel loci. The findings highlight both genetic similarities and population-specific variations in SNPs influencing IOP and provide valuable insights to enhance eye health care, including glaucoma management.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

查看原文本刊更多论文

日本以人群为基础的队列中眼压的全基因组关联研究：东北医学大库组织眼科研究

目的本研究旨在阐明眼部生物特征参数的分布和决定因素，并评估眼压（IOP）与日本人群基因组队列研究中单核苷酸多态性（snp）之间的关系。涉及全基因组关联研究（GWASs）的横断面分析。参与者共检查了来自人口队列（社区队列[CommCohort]）的22 150名18岁参与者和来自东北医学大库组织眼科研究的出生和三代（BirThree）队列的11 302名参与者。方法对患者进行访谈、眼科和生理检查、实验室检查和芯片分析。在CommCohort（发现阶段）和BirThree Cohort（复制阶段）中进行全基因组关联研究，然后进行meta分析。使用全基因组显著性阈值（5 × 10−8）评估snp与IOP的关联。snp与IOP的关系以及IOP的性别和年龄分布。结果发现期右眼和左眼平均眼压分别为13.95和14.02 mmHg。在复制阶段，相应的值分别为14.32和14.27 mmHg。在两个阶段均观察到明显的年龄相关性IOP降低(P <；0.001)。全基因组关联研究分别在发现和复制阶段发现了573个和2个全基因组显著snp。荟萃分析显示，在11条染色体（Chrs）的21个位点上存在1601个显著snp。在这些基因座中，先前已知有17个与IOP或青光眼相关，而4个SEPT8 (SEPT8；Chr5)，醛脱氢酶2 (ALDH2；Chr12)， VI型胶原α 2链(COL6A2；Chr21)和Wnt家族成员7B (WNT7B；Chr22) -是新发现的。结论在日本人群中进行的大规模GWAS鉴定出21个与IOP相关的位点，其中包括4个新位点。该研究结果强调了影响IOP的snp的遗传相似性和人群特异性差异，并为加强眼保健，包括青光眼管理提供了有价值的见解。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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