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Original Investigation
June 3, 2021

Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population

Author Affiliations
  • 1Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
  • 2Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland
  • 3Finnish Institute for Health and Welfare, Helsinki, Finland
  • 4Department of Ophthalmology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
  • 5TAYS Eye Center, Tampere University and Tampere University Hospital, Tampere, Finland
  • 6Department of Obstetrics and Gynecology, Tampere University and Tampere University Hospital, Tampere, Finland
  • 7Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
JAMA Ophthalmol. Published online June 3, 2021. doi:10.1001/jamaophthalmol.2021.1610
Key Points

Question  What is the association of the common MYOC p.(Gln368Ter) variant with different types of glaucoma in a Finnish population where the variant is highly enriched?

Findings  This genetic association study found that individuals with heterozygous MYOC p.(Gln368Ter) genotype had higher odds of primary open-angle glaucoma, exfoliation glaucoma, and glaucoma-related operations. The association could not be replicated with normal-tension glaucoma.

Meaning  This study found that the MYOC p.(Gln368Ter) variant was associated with glaucoma subtypes with increased intraocular pressure, including exfoliation glaucoma.


Importance  The c.1102C>T, p.(Gln368Ter) variant in the myocilin (MYOC) gene is a known risk allele for glaucoma. It is the most common MYOC risk variant for glaucoma among individuals of European ancestry, and its prevalence is highest in Finland. Furthermore, exfoliation syndrome has high prevalence in Scandinavia, making the Finnish population ideal to study the association of the variant with different types of glaucoma.

Objectives  To examine the association and penetrance of MYOC p.(Gln368Ter) (rs74315329) variant with different types of glaucoma in a Finnish population.

Design, Setting, and Participants  This genetic association study included individuals of Finnish ancestry in the FinnGen project. The participants were collected from Finnish biobanks, and the disease end points were defined using nationwide registries. The MYOC c.1102C>T variant was either directly genotyped or imputed with microarrays. Recruitment of samples to FinnGen was initiated in 2017, and data analysis was performed between December 2019 and May 2020.

Main Outcomes and Measures  The main outcomes were odds ratios (ORs) and penetrance with different types of glaucoma and in different age groups.

Results  A total of 218 792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123 579 women [56.5%]), including 8591 (3.9%) with glaucoma, 3412 (1.6%) with primary open-angle glaucoma, 1515 (0.7%) with exfoliation glaucoma, 892 (0.4%) with normal-tension glaucoma, and 4766 (2.2%) with suspected glaucoma. The minor allele frequency of MYOC p.(Gln368Ter) was 0.28%. Individuals with the heterozygous variant had higher odds of primary open-angle glaucoma (OR, 3.36; 95% CI, 2.55-4.37), overall glaucoma (OR, 2.58; 95% CI, 2.12-3.13), suspected glaucoma (OR, 2.53; 95% CI, 1.93-3.26), exfoliation glaucoma (OR, 2.61; 95% CI, 1.60-4.02), and undergoing glaucoma-related operations (OR, 5.45; 95% CI, 2.95-9.28). The penetrance of heterozygous MYOC p.(Gln368Ter) was 5.2% in individuals with primary open-angle glaucoma, 9.6% in individuals with glaucoma, 5.4% in individuals with suspected glaucoma, and 1.9% in individuals with exfoliation glaucoma. There was no significant association with normal-tension glaucoma (OR, 1.69; 95% CI, 0.72-3.35).

Conclusions and Relevance  This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population.

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