Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.
AL, axial length
Axial length
BirThree, birth and three-generation cohort
CommCohort, community-based cohort
GWAS, genome-wide association study
Genome-wide association study
MAF, minor allele frequency
PCA, principal component analysis
Population-based cohort study
TMM, Tohoku Medical Megabank
ToMMo, Tohoku Medical Megabank Organization
Journal
Ophthalmology science
ISSN: 2666-9145
Titre abrégé: Ophthalmol Sci
Pays: Netherlands
ID NLM: 9918230896206676
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
08
06
2021
revised:
07
01
2022
accepted:
07
01
2022
entrez:
17
10
2022
pubmed:
18
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
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. We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). 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. 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 We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. 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 ( 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.
Identifiants
pubmed: 36246171
doi: 10.1016/j.xops.2022.100113
pii: S2666-9145(22)00002-1
pmc: PMC9559092
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100113Informations de copyright
© 2022 by the American Academy of Ophthalmology.
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