TY - JOUR
T1 - Association of the MYOC p.(Gln368Ter) Variant with Glaucoma in a Finnish Population
AU - Liuska, Perttu J.
AU - Lemmelä, Susanna
AU - Havulinna, Aki S.
AU - Kaarniranta, Kai
AU - Uusitalo, Hannu
AU - Laivuori, Hannele
AU - Kiiskinen, Tuomo
AU - Daly, Mark J.
AU - Palotie, Aarno
AU - Turunen, Joni A.
N1 - Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/6/3
Y1 - 2021/6/3
N2 - 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 218792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123579 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..
AB - 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 218792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123579 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..
U2 - 10.1001/jamaophthalmol.2021.1610
DO - 10.1001/jamaophthalmol.2021.1610
M3 - Article
C2 - 34081096
AN - SCOPUS:85107771764
SN - 2168-6165
VL - 139
SP - 762
EP - 768
JO - JAMA OPHTHALMOLOGY
JF - JAMA OPHTHALMOLOGY
IS - 7
ER -