Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan

Nobuo Fuse, MD, PhD; Miyuki Sakurai, PhD; Ikuko N. Motoike, PhD; Kaname Kojima, PhD; Takako Takai-Igarashi, PhD; Naoki Nakaya, PhD; Naho Tsuchiya, MD, PhD; Tomohiro Nakamura, PhD; Mami Ishikuro, PhD; Taku Obara, PhD; Akiko Miyazawa, MD, PhD; Kei Homma, MD, PhD; Keisuke Ido, PhD; Makiko Taira, MD, PhD; Tomoko Kobayashi, MD, PhD; Ritsuko Shimizu, MD, PhD; Akira Uruno, MD, PhD; Eiichi N. Kodama, MD, PhD; Kichiya Suzuki, MD, PhD; Yohei Hamanaka, MD, PhD; Hiroaki Tomita, MD, PhD; Junichi Sugawara, MD, PhD; Yoichi Suzuki, MD, PhD; Fuji Nagami, PhD; Soichi Ogishima, PhD; Fumiki Katsuoka, PhD; Naoko Minegishi, MD, PhD; Atsushi Hozawa, MD, PhD; Shinichi Kuriyama, MD, PhD; Nobuo Yaegashi, MD, PhD; Shigeo Kure, MD, PhD; Kengo Kinoshita, PhD; Masayuki Yamamoto, MD, PhD

Ophthalmology Science (Mar 2022)

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan

Nobuo Fuse, MD, PhD,
Miyuki Sakurai, PhD,
Ikuko N. Motoike, PhD,
Kaname Kojima, PhD,
Takako Takai-Igarashi, PhD,
Naoki Nakaya, PhD,
Naho Tsuchiya, MD, PhD,
Tomohiro Nakamura, PhD,
Mami Ishikuro, PhD,
Taku Obara, PhD,
Akiko Miyazawa, MD, PhD,
Kei Homma, MD, PhD,
Keisuke Ido, PhD,
Makiko Taira, MD, PhD,
Tomoko Kobayashi, MD, PhD,
Ritsuko Shimizu, MD, PhD,
Akira Uruno, MD, PhD,
Eiichi N. Kodama, MD, PhD,
Kichiya Suzuki, MD, PhD,
Yohei Hamanaka, MD, PhD,
Hiroaki Tomita, MD, PhD,
Junichi Sugawara, MD, PhD,
Yoichi Suzuki, MD, PhD,
Fuji Nagami, PhD,
Soichi Ogishima, PhD,
Fumiki Katsuoka, PhD,
Naoko Minegishi, MD, PhD,
Atsushi Hozawa, MD, PhD,
Shinichi Kuriyama, MD, PhD,
Nobuo Yaegashi, MD, PhD,
Shigeo Kure, MD, PhD,
Kengo Kinoshita, PhD,
Masayuki Yamamoto, MD, PhD

Affiliations

Nobuo Fuse, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Correspondence: Nobuo Fuse, MD, PhD, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
Miyuki Sakurai, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Ikuko N. Motoike, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Kaname Kojima, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Takako Takai-Igarashi, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Naoki Nakaya, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Naho Tsuchiya, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Tomohiro Nakamura, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Mami Ishikuro, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Taku Obara, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Akiko Miyazawa, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Kei Homma, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Keisuke Ido, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Makiko Taira, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Tomoko Kobayashi, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Ritsuko Shimizu, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Akira Uruno, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Eiichi N. Kodama, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; International Research Institute of Disaster Science, Tohoku University, Sendai, Japan
Kichiya Suzuki, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Yohei Hamanaka, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Hiroaki Tomita, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Junichi Sugawara, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Yoichi Suzuki, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Fuji Nagami, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Soichi Ogishima, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan
Fumiki Katsuoka, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan
Naoko Minegishi, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Atsushi Hozawa, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Shinichi Kuriyama, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; International Research Institute of Disaster Science, Tohoku University, Sendai, Japan
Nobuo Yaegashi, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Shigeo Kure, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan
Kengo Kinoshita, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Japan; Department of System Bioinformatics, Tohoku University Graduate School of Information Sciences, Sendai, Japan
Masayuki Yamamoto, MD, PhD: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Graduate School of Medicine, Sendai, Japan

Journal volume & issue: Vol. 2, no. 1
p. 100113

Abstract

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Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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