Journal Article Epublish
PubMed: 40584246 DOI: 10.1016/j.xops.2025.100821
Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.
Ophthalmol Sci 5(5):100821
Authors: Nobuo Fuse, Hayato Anzawa, Miyuki Sakurai, Ikuko N Motoike, Satoshi Nagaie, Tomohiro Nakamura, Akiko Miyazawa, Eiichi N Kodama, Masatsugu Orui, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Makiko Taira, Ritsuko Shimizu, Naoki Nakaya, Mami Ishikuro, Taku Obara, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Kazuki Kumada, Shinichi Kuriyama, Atsushi Hozawa, Yoko Izumi, Kengo Kinoshita, Masayuki Yamamoto
Affiliations
- Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
- Department of System Bioinformatics, Tohoku University Graduate School of Information Sciences, Sendai, Japan.
- Department of Data Science, Kyoto Women's University, Kyoto, Japan.
- Tohoku University International Research Institute of Disaster Science, Sendai, Japan.
- Tohoku University Graduate School of Medicine, Sendai, Japan.
- Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan.
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 Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
MeSH
Eye, Cross-Sectional Studies, Genome-Wide Association Study, Genome, Glaucoma, Collagen Type Vi, Polymorphism, Single Nucleotide, Intraocular Pressure