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

2021; American Medical Association; Volume: 139; Issue: 7 Linguagem: Inglês

10.1001/jamaophthalmol.2021.1610

2168-6173

Perttu J. Liuska, Susanna Lemmelä, Aki S. Havulinna, Kai Kaarniranta, Hannu Uusitalo, Hannele Laivuori, Tuomo Kiiskinen, Mark J. Daly, Aarno Palotie, Joni A. Turunen, Howard J. Jacob, Athena Matakidou, Heiko Runz, Sally John, Robert Plenge, Julie Hunkapiller, Meg Ehm, Dawn Waterworth, Caroline S. Fox, Anders Mälarstig, Kathy Klinger, Kathy Call, Tomi P. Mäkelä, Jaakko Kaprio, Petri Virolainen, Kari Pulkki, Terhi Kilpi, Markus Perola, Jukka Partanen, Anne Pitkäranta, Riitta Kaarteenaho, Seppo Vainio, Kimmo Savinainen, Veli‐Matti Kosma, Urho M. Kujala, Jeff Waring, Bridget Riley‐Gillis, Jiang Liu, Shameek Biswas, J. M. Hoffman, Dorothée Diogo, Catherine Marshall, Xinli Hu, Samuli Ripatti, Johanna Schleutker, Tiina Wahlfors, Olli Carpén, Johanna Myllyharju, Johannes Kettunen, Reijo Laaksonen, Arto Mannermaa, Juha Paloneva, Hilkka Soininen, Valtteri Julkunen, Anne M. Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha O. Rinne, Adam Ziemann, Jeffrey F. Waring, Sahar Esmaeeli, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Janet van Adelsberg, John A. Michon, Geoff Kerchner, Natalie Bowers, Edmond Teng, John D. Eicher, Vinay Mehta, Padhraig Gormley, Kari Linden, Christopher D. Whelan, Fanli Xu, David Pulford, Martti Färkkilâ, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Bob Georgantas, Graham Heap, Fedik Rahimov, Keith Usiskin, Tim Lu, Danny Oh, Dermot F. Reilly, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari K. Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Oili Kaipiainen‐Seppänen, Johanna Huhtakangas, Apinya Lertratanakul, David A. Close, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Dirk S. Paul, Hannu Kankaanranta, Terttu Harju, Steven Greenberg, Hubert Chen, Jo Betts, Soumitra Ghosh, Veikko Salomaa, Teemu Niiranen, Markus Juonala, Kaj Metsärinne, Mika Kähönen, Juhani Junttila, Markku Laakso, Jussi Pihlajamäki, Juha Sinisalo, Marja‐Riitta Taskinen, Jaakko Tuomilehto, Jari A. Laukkanen, Ben Challis, Andrew S. Peterson, Audrey Y. Chu, Jaakko Parkkinen, Anthony J. Muslin, Heikki Joensuu, Tuomo J Meretoja, Lauri A. Aaltonen, Annika Auranen, Peeter Karihtala, Saila Kauppila, Päivi Auvinen, Klaus Elenius, Relja Popovic, Jennifer L. Schutzman, Andrey Loboda, Aparna Chhibber, Heli Lehtonen, Stefan McDonough, Marika Crohns, Diptee Kulkarni, Terhi Ollila, Sanna Seitsonen, Vesa Aaltonen, Hannele Uusitalo‐Järvinen, Marja Luodonpää, Nina Hautala, Erich C. Strauss, Hao Chen, Anna Podgornaia, Joshua Hoffman, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, Ilkka T. Harvima, Ying Wu, David F. Choy, Anu Jalanko, Risto Kajanne, Ulrike Lyhs, Mari Kaunisto, J. Wade Davis, Danjuma Quarless, Slavé Petrovski, Chia‐Yen Chen, Paola G. Bronson, Robert Yang, Joseph Maranville, Diana Chang, Tushar Bhangale, Emily Holzinger, Xulong Wang, Xing Chen, Åsa K. Hedman, Clarence Wang, Ethan Xu, Franck Augé, Clément Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Pietro Della Briotta Parolo, Wei Zhou, Manuel A. Rivas, Jarmo Harju, Arto Lehistö, Andrea Ganna, Vincent Llorens, Antti Karlsson, Kati Kristiansson, Mikko Arvas, Kati Hyvärinen, Jarmo Ritari, Miika Koskinen, Katri Pylkäs, Marita Kalaoja, Minna K. Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija K. Laakkonen, Juha Kononen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Tero Hiekkalinna, Manuel González Jiménez, Kati Donner, Kalle Pärn, Javier Núñez-Fontarnau, Elina Kilpeläinen, Timo P. Sipilä, Georg Brein, Alexander Dada, Anastasia Shcherban, Tuomas Sipilä, Harri Siirtola, Javier Gracia‐Tabuenca, Lila Kallio, Sirpa Soini, Kimmo Pitkänen, Teijo Kuopio,

Proteoglycans and glycosaminoglycans research

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.To examine the association and penetrance of MYOC p.(Gln368Ter) (rs74315329) variant with different types of glaucoma in a Finnish population.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.The main outcomes were odds ratios (ORs) and penetrance with different types of glaucoma and in different age groups.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).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.