Search

Your search keyword '"Astakhov, Yury S"' showing total 37 results
Start Over Author "Astakhov, Yury S"
37 results on '"Astakhov, Yury S"'

1. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Author

Aung, Tin, Ozaki, Mineo, Lee, Mei Chin, Schlötzer-Schrehardt, Ursula, Thorleifsson, Gudmar, Mizoguchi, Takanori, Igo, Robert P, Haripriya, Aravind, Williams, Susan E, Astakhov, Yury S, Orr, Andrew C, Burdon, Kathryn P, Nakano, Satoko, Mori, Kazuhiko, Abu-Amero, Khaled, Hauser, Michael, Li, Zheng, Prakadeeswari, Gopalakrishnan, Bailey, Jessica N Cooke, Cherecheanu, Alina Popa, Kang, Jae H, Nelson, Sarah, Hayashi, Ken, Manabe, Shin-ichi, Kazama, Shigeyasu, Zarnowski, Tomasz, Inoue, Kenji, Irkec, Murat, Coca-Prados, Miguel, Sugiyama, Kazuhisa, Järvelä, Irma, Schlottmann, Patricio, Lerner, S Fabian, Lamari, Hasnaa, Nilgün, Yildirim, Bikbov, Mukharram, Park, Ki Ho, Cha, Soon Cheol, Yamashiro, Kenji, Zenteno, Juan C, Jonas, Jost B, Kumar, Rajesh S, Perera, Shamira A, Chan, Anita SY, Kobakhidze, Nino, George, Ronnie, Vijaya, Lingam, Do, Tan, Edward, Deepak P, de Juan Marcos, Lourdes, Pakravan, Mohammad, Moghimi, Sasan, Ideta, Ryuichi, Bach-Holm, Daniella, Kappelgaard, Per, Wirostko, Barbara, Thomas, Samuel, Gaston, Daniel, Bedard, Karen, Greer, Wenda L, Yang, Zhenglin, Chen, Xueyi, Huang, Lulin, Sang, Jinghong, Jia, Hongyan, Jia, Liyun, Qiao, Chunyan, Zhang, Hui, Liu, Xuyang, Zhao, Bowen, Wang, Ya-Xing, Xu, Liang, Leruez, Stéphanie, Reynier, Pascal, Chichua, George, Tabagari, Sergo, Uebe, Steffen, Zenkel, Matthias, Berner, Daniel, Mossböck, Georg, Weisschuh, Nicole, Hoja, Ursula, Welge-Luessen, Ulrich-Christoph, Mardin, Christian, Founti, Panayiota, Chatzikyriakidou, Anthi, Pappas, Theofanis, Anastasopoulos, Eleftherios, Lambropoulos, Alexandros, Ghosh, Arkasubhra, Shetty, Rohit, Porporato, Natalia, Saravanan, Vijayan, Venkatesh, Rengaraj, Shivkumar, Chandrashekaran, Kalpana, Narendran, Sarangapani, Sripriya, Kanavi, Mozhgan R, Beni, Afsaneh Naderi, and Yazdani, Shahin

Subjects
Prevention, Human Genome, Rare Diseases, Genetics, Aetiology, 2.1 Biological and endogenous factors, Aged, 80 and over, Alleles, Amino Acid Oxidoreductases, Amino Acid Substitution, Asian People, Calcium Channels, Cell Adhesion, Exfoliation Syndrome, Extracellular Matrix, Eye, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Humans, Male, Molecular Chaperones, Mutation, Missense, Point Mutation, RNA, Messenger, Spheroids, Cellular, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Published
2017

2. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome

Author

Aung, Tin, Ozaki, Mineo, Mizoguchi, Takanori, Allingham, R Rand, Li, Zheng, Haripriya, Aravind, Nakano, Satoko, Uebe, Steffen, Harder, Jeffrey M, Chan, Anita SY, Lee, Mei Chin, Burdon, Kathryn P, Astakhov, Yury S, Abu-Amero, Khaled K, Zenteno, Juan C, Nilgün, Yildirim, Zarnowski, Tomasz, Pakravan, Mohammad, Safieh, Leen Abu, Jia, Liyun, Wang, Ya Xing, Williams, Susan, Paoli, Daniela, Schlottmann, Patricio G, Huang, Lulin, Sim, Kar Seng, Foo, Jia Nee, Nakano, Masakazu, Ikeda, Yoko, Kumar, Rajesh S, Ueno, Morio, Manabe, Shin-ichi, Hayashi, Ken, Kazama, Shigeyasu, Ideta, Ryuichi, Mori, Yosai, Miyata, Kazunori, Sugiyama, Kazuhisa, Higashide, Tomomi, Chihara, Etsuo, Inoue, Kenji, Ishiko, Satoshi, Yoshida, Akitoshi, Yanagi, Masahide, Kiuchi, Yoshiaki, Aihara, Makoto, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Matsuda, Fumihiko, Yamashiro, Kenji, Gotoh, Norimoto, Miyake, Masahiro, Astakhov, Sergei Y, Osman, Essam A, Al-Obeidan, Saleh A, Owaidhah, Ohoud, Al-Jasim, Leyla, Shahwan, Sami Al, Fogarty, Rhys A, Leo, Paul, Yetkin, Yaz, Oğuz, Çilingir, Kanavi, Mozhgan Rezaei, Beni, Afsaneh Naderi, Yazdani, Shahin, Akopov, Evgeny L, Toh, Kai-Yee, Howell, Gareth R, Orr, Andrew C, Goh, Yufen, Meah, Wee Yang, Peh, Su Qin, Kosior-Jarecka, Ewa, Lukasik, Urszula, Krumbiegel, Mandy, Vithana, Eranga N, Wong, Tien Yin, Liu, Yutao, Koch, Allison E Ashley, Challa, Pratap, Rautenbach, Robyn M, Mackey, David A, Hewitt, Alex W, Mitchell, Paul, Wang, Jie Jin, Ziskind, Ari, Carmichael, Trevor, Ramakrishnan, Rangappa, Narendran, Kalpana, Venkatesh, Rangaraj, Vijayan, Saravanan, Zhao, Peiquan, Chen, Xueyi, Guadarrama-Vallejo, Dalia, Cheng, Ching Yu, Perera, Shamira A, Husain, Rahat, and Ho, Su-Ling

Subjects
Biological Sciences, Genetics, Rare Diseases, Human Genome, Prevention, 2.1 Biological and endogenous factors, Aetiology, Animals, Asian People, Calcium Channels, Case-Control Studies, Chromosome Mapping, Exfoliation Syndrome, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, HEK293 Cells, HeLa Cells, Humans, Japan, MCF-7 Cells, Mice, Mice, Inbred C57BL, Polymorphism, Single Nucleotide, Tumor Cells, Cultured, Blue Mountains Eye Study GWAS Team, Wellcome Trust Case Control Consortium 2, Hela Cells, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Published
2015

3. Zygomaticoorbital Fractures

Author

Nikolaenko, Vadim P., Astakhov, Yury S., Soloviev, Mikhail M., Khatskevich, G., Trofimov, Igor G., Nikolaenko, Vadim P., editor, and Astakhov, Yury S., editor

Published
2015
Full Text
View/download PDF

4. Frontobasilar Fractures

Author

Nikolaenko, Vadim P., Astakhov, Yury S., Shulev, Yury A., Karpischenko, Sergei A., Nikolaenko, Vadim P., editor, and Astakhov, Yury S., editor

Published
2015
Full Text
View/download PDF

5. Radiological Examination of the Orbit

Author

Nikolaenko, Vadim P., Astakhov, Yury S., Trufanov, Gennadiy E., Burlachenko, Evgeniy P., Zakharov, Valery V., Lugina, Valentina D., Nikolaenko, Vadim P., editor, and Astakhov, Yury S., editor

Published
2015
Full Text
View/download PDF

6. Maxillary Fractures

Author

Nikolaenko, Vadim P., Astakhov, Yury S., Soloviev, Mikhail M., Khatskevich, G., Trofimov, Igor G., Nikolaenko, Vadim P., editor, and Astakhov, Yury S., editor

Published
2015
Full Text
View/download PDF

8. Medial Wall Fractures

Author

Nikolaenko, Vadim P., Astakhov, Yury S., Karpischenko, Sergei A., Nikolaenko, Vadim P., editor, and Astakhov, Yury S., editor

Published
2015
Full Text
View/download PDF

11. Association of Rare CYP39A1 Variants with Exfoliation Syndrome Involving the Anterior Chamber of the Eye

Author

Li, Zheng, Wang, Zhenxun, Lee, Mei Chin, Zenkel, Matthias, Peh, Esther, Ozaki, Mineo, Topouzis, Fotis, Nakano, Satoko, Chan, Anita, Chen, Shuwen, Williams, Susan E.I., Orr, Andrew, Nakano, Masakazu, Kobakhidze, Nino, Zarnowski, Tomasz, Popa-Cherecheanu, Alina, Mizoguchi, Takanori, Manabe, Shin Ichi, Hayashi, Ken, Kazama, Shigeyasu, Inoue, Kenji, Mori, Yosai, Miyata, Kazunori, Sugiyama, Kazuhisa, Higashide, Tomomi, Chihara, Etsuo, Ideta, Ryuichi, Ishiko, Satoshi, Yoshida, Akitoshi, Tokumo, Kana, Kiuchi, Yoshiaki, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Aihara, Makoto, Inatani, Masaru, Mori, Kazuhiko, Ikeda, Yoko, Ueno, Morio, Gaston, Daniel, Rafuse, Paul, Shuba, Lesya, Saunders, Joseph, Nicolela, Marcelo, Chichua, George, Tabagari, Sergo, Founti, Panayiota, Sim, Kar Seng, Meah, Wee Yang, Soo, Hui Meng, Chen, Xiao Yin, Chatzikyriakidou, Anthi, Keskini, Christina, Pappas, Theofanis, Anastasopoulos, Eleftherios, Lambropoulos, Alexandros, Panagiotou, Evangelia S., Mikropoulos, Dimitrios G., Kosior-Jarecka, Ewa, Cheong, Augustine, Li, Yuanhan, Lukasik, Urszula, Nongpiur, Monisha E., Husain, Rahat, Perera, Shamira A., Álvarez, Lydia, García, Montserrat, González-Iglesias, Héctor, Cueto, Andrés F.V., Cueto, Luis F.V., Martinón-Torres, Federico, Salas, Antonio, Oguz, Çilingir, Tamcelik, Nevbahar, Atalay, Eray, Batu, Bilge, Irkec, Murat, Aktas, Dilek, Kasim, Burcu, Astakhov, Yury S., Astakhov, Sergei Y., Akopov, Eugeny L., Giessl, Andreas, Mardin, Christian, Hellerbrand, Claus, Cooke Bailey, Jessica N., Igo, Robert P., Haines, Jonathan L., Edward, Deepak P., Heegaard, Steffen, Davila, Sonia, Tan, Patrick, Kang, Jae H., Pasquale, Louis R., Kruse, Friedrich E., Reis, André, Carmichael, Trevor R., Hauser, Michael, Ramsay, Michele, Mossböck, Georg, Yildirim, Nilgun, Tashiro, Kei, Konstas, Anastasios G.P., Coca-Prados, Miguel, Foo, Jia Nee, Kinoshita, Shigeru, Sotozono, Chie, Kubota, Toshiaki, Dubina, Michael, Ritch, Robert, Wiggs, Janey L., Pasutto, Francesca, Schlötzer-Schrehardt, Ursula, Ho, Ying Swan, Aung, Tin, Tam, Wai Leong, Khor, Chiea Chuen, Li, Zheng, Wang, Zhenxun, Lee, Mei Chin, Zenkel, Matthias, Peh, Esther, Ozaki, Mineo, Topouzis, Fotis, Nakano, Satoko, Chan, Anita, Chen, Shuwen, Williams, Susan E.I., Orr, Andrew, Nakano, Masakazu, Kobakhidze, Nino, Zarnowski, Tomasz, Popa-Cherecheanu, Alina, Mizoguchi, Takanori, Manabe, Shin Ichi, Hayashi, Ken, Kazama, Shigeyasu, Inoue, Kenji, Mori, Yosai, Miyata, Kazunori, Sugiyama, Kazuhisa, Higashide, Tomomi, Chihara, Etsuo, Ideta, Ryuichi, Ishiko, Satoshi, Yoshida, Akitoshi, Tokumo, Kana, Kiuchi, Yoshiaki, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Aihara, Makoto, Inatani, Masaru, Mori, Kazuhiko, Ikeda, Yoko, Ueno, Morio, Gaston, Daniel, Rafuse, Paul, Shuba, Lesya, Saunders, Joseph, Nicolela, Marcelo, Chichua, George, Tabagari, Sergo, Founti, Panayiota, Sim, Kar Seng, Meah, Wee Yang, Soo, Hui Meng, Chen, Xiao Yin, Chatzikyriakidou, Anthi, Keskini, Christina, Pappas, Theofanis, Anastasopoulos, Eleftherios, Lambropoulos, Alexandros, Panagiotou, Evangelia S., Mikropoulos, Dimitrios G., Kosior-Jarecka, Ewa, Cheong, Augustine, Li, Yuanhan, Lukasik, Urszula, Nongpiur, Monisha E., Husain, Rahat, Perera, Shamira A., Álvarez, Lydia, García, Montserrat, González-Iglesias, Héctor, Cueto, Andrés F.V., Cueto, Luis F.V., Martinón-Torres, Federico, Salas, Antonio, Oguz, Çilingir, Tamcelik, Nevbahar, Atalay, Eray, Batu, Bilge, Irkec, Murat, Aktas, Dilek, Kasim, Burcu, Astakhov, Yury S., Astakhov, Sergei Y., Akopov, Eugeny L., Giessl, Andreas, Mardin, Christian, Hellerbrand, Claus, Cooke Bailey, Jessica N., Igo, Robert P., Haines, Jonathan L., Edward, Deepak P., Heegaard, Steffen, Davila, Sonia, Tan, Patrick, Kang, Jae H., Pasquale, Louis R., Kruse, Friedrich E., Reis, André, Carmichael, Trevor R., Hauser, Michael, Ramsay, Michele, Mossböck, Georg, Yildirim, Nilgun, Tashiro, Kei, Konstas, Anastasios G.P., Coca-Prados, Miguel, Foo, Jia Nee, Kinoshita, Shigeru, Sotozono, Chie, Kubota, Toshiaki, Dubina, Michael, Ritch, Robert, Wiggs, Janey L., Pasutto, Francesca, Schlötzer-Schrehardt, Ursula, Ho, Ying Swan, Aung, Tin, Tam, Wai Leong, and Khor, Chiea Chuen

Abstract

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The fi

Published
2021

14. Noninferiority of Preservative-free Versus BAK-preserved Latanoprost-timolol Fixed Combination Eye Drops in Patients With Open-angle Glaucoma or Ocular Hypertension

Author

Aptel, Florent, primary, Pfeiffer, Norbert, additional, Schmickler, Stefanie, additional, Clarke, Jonathan, additional, Lavín-Dapena, Cosme, additional, Moreno-Montañés, Javier, additional, Żarnowski, Tomasz, additional, Csutak, Adrienne, additional, Jugaste, Tiia, additional, Volksone, Lāsma, additional, Astakhov, Yury S., additional, Coupier, Laurent, additional, Nordmann, Jean-Philippe, additional, and Stalmans, Ingeborg, additional

Published
2019
Full Text
View/download PDF

15. The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome

Author

Berner, Daniel, primary, Hoja, Ursula, additional, Zenkel, Matthias, additional, Ross, James Julian, additional, Uebe, Steffen, additional, Paoli, Daniela, additional, Frezzotti, Paolo, additional, Rautenbach, Robyn M, additional, Ziskind, Ari, additional, Williams, Susan E, additional, Carmichael, Trevor R, additional, Ramsay, Michele, additional, Topouzis, Fotis, additional, Chatzikyriakidou, Anthi, additional, Lambropoulos, Alexandros, additional, Sundaresan, Periasamy, additional, Ayub, Humaira, additional, Akhtar, Farah, additional, Qamar, Raheel, additional, Zenteno, Juan C, additional, Cruz-Aguilar, Marisa, additional, Astakhov, Yury S, additional, Dubina, Michael, additional, Wiggs, Janey, additional, Ozaki, Mineo, additional, Kruse, Friedrich E, additional, Aung, Tin, additional, Reis, André, additional, Khor, Chiea Chuen, additional, Pasutto, Francesca, additional, and Schlötzer-Schrehardt, Ursula, additional

Published
2019
Full Text
View/download PDF

21. Retinal astrocytic hamartoma in tuberous sclerosis

Author

Astakhov, Yury S, primary, Nechiporenko, Pavel A, additional, Atlasova, Liya K, additional, Titarenko, Aleksandra I, additional, Monakhov, Konstantin N, additional, Romanova, Oksana L, additional, and Molodykh, Kristina Y, additional

Published
2017
Full Text
View/download PDF

23. Erratum: A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome (Nature Genetics (2015) 47 (387-392))

Author

Aung, Tin, Ozaki, Mineo, Mizoguchi, Takanori, Allingham, R. Rand, Zheng, Li, Haripriya, Aravind, Nakano, Satoko, Uebe, Steffen, Harder, Jeffrey M., Chan, Anita S. Y., Lee, Mei Chin, Burdon, Kathryn P., Astakhov, Yury S., Abu Amero, Khaled K., Zenteno, Juan C., Nilgün, Yildirim, Zarnowski, Tomasz, Pakravan, Mohammad, Safieh, Leen Abu, Jia, Liyun, Wang, Ya Xing, Williams, Susan, Paoli, Daniela, Schlottmann, Patricio G., Huang, Lulin, Sim, Kar Seng, Foo, Jia Nee, Nakano, Masakazu, Ikeda, Yoko, Kumar, Rajesh S., Ueno, Morio, Manabe, Shin Ichi, Hayashi, Ken, Kazama, Shigeyasu, Ideta, Ryuichi, Mori, Yosai, Miyata, Kazunori, Sugiyama, Kazuhisa, Higashide, Tomomi, Chihara, Etsuo, Inoue, Kenji, Ishiko, Satoshi, Yoshida, Akitoshi, Yanagi, Masahide, Kiuchi, Yoshiaki, Aihara, Makoto, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Matsuda, Fumihiko, Yamashiro, Kenji, Gotoh, Norimoto, Miyake, Masahiro, Astakhov, Sergei Y., Osman, Essam A., Al Obeidan, Saleh A., Owaidhah, Ohoud, Al Jasim, Leyla, Shahwan, Sami Al, Fogarty, Rhys A., Leo, Paul, Yetkin, Yaz, Oaiuz, Çilingir, Kanavi, Mozhgan Rezaei, Beni, Afsaneh Naderi, Yazdani, Shahin, Akopov, Evgeny L., Toh, Kai Yee, Howell, Gareth R., Orr, Andrew C., Goh, Yufen, Meah, Wee Yang, Peh, Su Qin, Kosior Jarecka, Ewa, Lukasik, Urszula, Krumbiegel, Mandy, Vithana, Eranga N., Wong, Tien Yin, Liu, Yutao, Koch, Allison E. Ashley, Challa, Pratap, Rautenbach, Robyn M., Mackey, David A., Hewitt, Alex W., Mitchell, Paul, Wang, Jie Jin, Ziskind, Ari, Carmichael, Trevor, Ramakrishnan, Rangappa, Narendran, Kalpana, Venkatesh, Rangaraj, Vijayan, Saravanan, Zhao, Peiquan, Chen, Xueyi, Guadarrama Vallejo, Dalia, Cheng, Ching Yu, Perera, Shamira A., Husain, Rahat, Su Ling, Ho, Welge Luessen, Ulrich Christoph, Mardin, Christian, Schloetzer Schrehardt, Ursula, Hillmer, Axel M., Herms, Stefan, Moebus, Susanne, Nöthen, Markus M., Weisschuh, Nicole, Shetty, Rohit, Ghosh, Arkasubhra, Teo, Yik Ying, Brown, Matthew A., Lischinsky, Ignacio, Crowston, Jonathan G., Coote, Michae, Zhao, Bowen, Sang, Jinghong, Zhang, Nihong, You, Qisheng, Vysochinskaya, Vera, Founti, Panayiota, Chatzikyriakidou, Anthoula, Lambropoulos, Alexandros, Anastasopoulos, Eleftherios, Coleman, Anne L., Wilson, M. Roy, Rhee, Douglas J., Kang, Jae Hee, May Bolchakova, Inna, Heegaard, Steffen, Mori, Kazuhiko, Alward, Wallace L. M., Jonas, Jost B., Liang, Xu, Liebmann, Jeffrey M., Chowbay, Balram, Schaeffeler, Elke, Schwab, Matthias, Lerner, Fabian, Wang, Ningli, Yang, Zhenglin, Frezzotti, Paolo, Kinoshita, Shigeru, Fingert, John H., Inatani, Masaru, Tashiro, Kei, Reis, André, Edward, Deepak P., Pasquale, Louis R., Kubota, Toshiaki, Wiggs, Janey L., Pasutto, Francesca, Topouzis, Fotis, Dubina, Michael, Craig, Jamie E., Yoshimura, Nagahisa, Sundaresan, Periasamy, John, Simon W. M., Ritch, Robert, Hauser, Michael A., and Khor, Chiea Chuen

Subjects
Genetics
Published
2015

24. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome

Author

Aung, Tin, Ozaki, Mineo, Mizoguchi, Takanori, Allingham, R Rand, Li, Zheng, Haripriya, Aravind, Nakano, Satoko, Uebe, Steffen, Harder, Jeffrey M, Chan, Anita S Y, Lee, Mei Chin, Burdon, Kathryn P, Astakhov, Yury S, Abu-Amero, Khaled K, Zenteno, Juan C, Nilgün, Yildirim, Zarnowski, Tomasz, Pakravan, Mohammad, Safieh, Leen Abu, Jia, Liyun, Wang, Ya Xing, Williams, Susan, Paoli, Daniela, Schlottmann, Patricio G, Huang, Lulin, Sim, Kar Seng, Foo, Jia Nee, Nakano, Masakazu, Ikeda, Yoko, Kumar, Rajesh S, Ueno, Morio, Manabe, Shin-ichi, Hayashi, Ken, Kazama, Shigeyasu, Ideta, Ryuichi, Mori, Yosai, Miyata, Kazunori, Sugiyama, Kazuhisa, Higashide, Tomomi, Chihara, Etsuo, Inoue, Kenji, Ishiko, Satoshi, Yoshida, Akitoshi, Yanagi, Masahide, Kiuchi, Yoshiaki, Aihara, Makoto, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Matsuda, Fumihiko, Yamashiro, Kenji, Gotoh, Norimoto, Miyake, Masahiro, Astakhov, Sergei Y, Osman, Essam A, Al-Obeidan, Saleh A, Owaidhah, Ohoud, Al-Jasim, Leyla, Al Shahwan, Sami, Fogarty, Rhys A, Leo, Paul, Yetkin, Yaz, Oguz, Çilingir, Kanavi, Mozhgan Rezaei, Beni, Afsaneh Nederi, Yazdani, Shahin, Akopov, Evgeny L, Toh, Kai-Yee, Howell, Gareth R, Orr, Andrew C, Goh, Yufen, Meah, Wee Yang, Peh, Su Qin, Kosior-Jarecka, Ewa, Lukasik, Urszula, Krumbiegel, Mandy, Vithana, Eranga N, Wong, Tien Yin, Liu, Yutao, Koch, Allison E Ashley, Challa, Pratap, Rautenbach, Robyn M, Mackey, David A, Hewitt, Alex W, Mitchell, Paul, Wang, Jie Jin, Ziskind, Ari, Carmichael, Trevor, Ramakrishnan, Rangappa, Narendran, Kalpana, Venkatesh, Rangaraj, Vijayan, Saravanan, Zhao, Peiquan, Chen, Xueyi, Guadarrama-Vallejo, Dalia, Cheng, Ching Yu, Perera, Shamira A, Husain, Rahat, Ho, Su-Ling, Welge-Luessen, Ulrich-Christoph, Mardin, Christian, Schloetzer-Schrehardt, Ursula, Hillmer, Axel M, Herms, Stefan, Moebus, Susanne, Nöthen, Markus M, Weisschuh, Nicole, Shetty, Rohit, Ghosh, Arkasubhra, Teo, Yik Ying, Brown, Matthew A, Lischinsky, Ignacio, Crowston, Jonathan G, Coote, Michael, Zhao, Bowen, Sang, Jinghong, Zhang, Nihong, You, Qisheng, Vysochinskaya, Vera, Founti, Panayiota, Chatzikyriakidou, Anthoula, Lambropoulos, Alexandros, Anastasopoulos, Eleftherios, Coleman, Anne L, Wilson, M Roy, Rhee, Douglas J, Kang, Jae Hee, May-Bolchakova, Inna, Heegaard, Steffen, Mori, Kazuhiko, Alward, Wallace L M, Jonas, Jost B, Xu, Liang, Liebmann, Jeffrey M, Chowbay, Balram, Schaeffeler, Elke, Schwab, Matthias, Lerner, Fabian, Wang, Ningli, Yang, Zhenglin, Frezzotti, Paolo, Kinoshita, Shigeru, Fingert, John H, Inatani, Masaru, Tashiro, Kei, Reis, André, Edward, Deepak P, Pasquale, Louis R, Kubota, Toshiaki, Wiggs, Janey L, Pasutto, Francesca, Topouzis, Fotis, Dubina, Michael, Craig, Jamie E, Yoshimura, Nagahisa, Sundaresan, Periasamy, John, Simon W M, Ritch, Robert, Hauser, Michael A, Khor, Chiea-Chuen, Rochtchina, Elena, Viswanathan, Ananth C, Wong, Tien Y, Xie, Jing, Sim, Xueling, Inouye, Michael, Holliday, Elizabeth G, Attia, John, Scott, Rodney J, Baird, Paul N, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Wood, Nicholas W, Spencer, Chris C A, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, and Whittaker, Pamela

Subjects
Asian Continental Ancestry Group, Pseudoexfoliation syndrome, Medizin, Locus (genetics), Genome-wide association study, Biology, Inbred C57BL, Exfoliation Syndrome, Polymorphism, Single Nucleotide, Article, Mice, Animals, Calcium Channels, Case-Control Studies, Chromosome Mapping, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, HEK293 Cells, HeLa Cells, Humans, Japan, MCF-7 Cells, Mice, Inbred C57BL, Tumor Cells, Cultured, Genetics, Asian People, medicine, SNP, Allele, Polymorphism, Cultured, Case-control study, Glaucoma, Odds ratio, Single Nucleotide, medicine.disease, eye diseases, Tumor Cells, Open-Angle, Etiology
Abstract

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Published
2014

27. Choroidal osteoma

Author

Astakhov, Yury S, primary, Astakhov, Sergey Yu, additional, Potemkin, Vitaly V, additional, Marchenko, Olga A, additional, Belekhova, Svetlana G, additional, and Ovnanyan, Andronik Yu, additional

Published
2016
Full Text
View/download PDF

29. Primary choroidal lymphoma

Author

Potemkin, Vitaly V, primary, Astakhov, Yury S, additional, Marchenko, Olga A, additional, Vinogradova, Yulia N, additional, Raskin, Grigory A, additional, and Ageeva, Elena V, additional

Published
2016
Full Text
View/download PDF

33. Corrigendum: A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Author

Aung, Tin, Ozaki, Mineo, Mizoguchi, Takanori, Allingham, R Rand, Li, Zheng, Haripriya, Aravind, Nakano, Satoko, Uebe, Steffen, Harder, Jeffrey M, Chan, Anita S Y, Lee, Mei Chin, Burdon, Kathryn P, Astakhov, Yury S, Abu-Amero, Khaled K, Zenteno, Juan C, Nilgün, Yildirim, Zarnowski, Tomasz, Pakravan, Mohammad, Safieh, Leen Abu, and Jia, Liyun

Subjects
EXFOLIATION syndrome, GENE mapping
Abstract

A correction to the article “A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome" that was published online on 23 February 2015 is presented regarding the spelling error in the name of one of the authors Afsaneh Naderi Beni.

Published
2015
Full Text
View/download PDF

34. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Author

Daniele Cusi, Etsuo Chihara, Leyla Al-Jasim, Ya Xing Wang, Tero Kivelä, Jinghong Sang, Adeyinka O. Ashaye, Bowen Zhao, Tan Do, Susanne Moebus, Ursula Schlötzer-Schrehardt, Shamira A. Perera, Augustine W O Cheong, Afsaneh Naderi Beni, Francisco A. Escudero-Domínguez, Yoshiaki Kiuchi, Tomomi Higashide, DS Klobassa, Friedrich E. Kruse, Nicole Weisschuh, Chunyan Qiao, Muhammad Imran Khan, Martin L. Hibberd, Arthur J. Sit, Jamie E Craig, Akitoshi Yoshida, Periasamy Sundaresan, Humaira Ayub, Kathryn P. Burdon, Jonathan G Crowston, Kazunori Miyata, Marisa Cruz-Aguilar, Markus M. Nöthen, Hasnaa Lamari, Michael A. Hauser, Louis R. Pasquale, Anneke I. den Hollander, Eija Vesti, Ursula Hoja, Raphael Q Soh, Burcu Kasım, Adeola O Onakoya, Rachel W. Kuchtey, Eugeny L. Akopov, Liang Xu, Juan Carlos Zenteno, Chaiwat Teekhasaenee, Saleh A. Al-Obeidan, Eleftherios Anastasopoulos, Anita S Y Chan, Nagahisa Yoshimura, John Kuchtey, Naris Kitnarong, Yaan Fun Chong, Boonsong Wanichwecharugruang, R.R. Fayzrakhmanov, Paul Mitchell, N Kalpana, Unnur Thorsteinsdottir, Kei Tashiro, Rajesh Kumar, Jin Wook Jeoung, Deepak P. Edward, Frederico Martinon-Torres, Bilge Batu, Anavaj Sakuntabhai, Robert N. Weinreb, Héctor González-Iglesias, Sasan Moghimi, Jia Nee Foo, Nkechi J Uche, Karen Curtin, Kenji Inoue, Lingam Vijaya, Makoto Aihara, Dilek Aktas, Norimoto Gotoh, Wasu Supakontanasan, Laura Dallorto, Takako Sugimoto, Jonathan L. Haines, Olusola Olawoye, Janey L. Wiggs, Sripriya Sarangapani, Craig J. Chaya, Theofanis Pappas, Fotis Topouzis, Eranga N. Vithana, Steffen Heegaard, Fridbert Jonasson, Kazuhiko Mori, Idakwo Ugbede, Hongyan Jia, Anthi Chatzikyriakidou, Robert P. Igo, Soon Cheol Cha, Yueming Chen, Su-Ling Ho, Zhenglin Yang, Jost B. Jonas, Francesca Pasutto, Ken Hayashi, Rahat Husain, Georg Mossböck, S Fabian Lerner, R. Rand Allingham, Priti Sahay, Fumihiko Matsuda, Yanin Suwan, Teresa Rolle, Robert Ritch, Peter Kraft, Trevor R. Carmichael, Kar Seng Sim, Raheel Qamar, Gordana Sunaric Megevand, Tomasz Zarnowski, Shazia Micheal, Scott Thomas, Paolo Frezzotti, Vera Vysochinskaya, Linda M. Zangwill, Alina Popa Cherecheanu, Tin Aung, Jessica N. Cooke Bailey, Kyu Hyung Park, Edward Dervan, Suhanya Okeke, Pablo Fornero, Sidi M Ezzouhairi, Pascal Reynier, Gudmar Thorleifsson, Michael V. Dubina, Kazuhisa Sugiyama, Sylvain Roy, Per Kappelgaard, Mineo Ozaki, Vijayan Saravanan, Carlo Lavia, Wenda L. Greer, Takanori Mizoguchi, Alireza Lashay, A. Binder, Daniel Berner, Su Qin Peh, Balram Chowbay, Nino Kobakhidze, Ifeoma N. Asimadu, Delia Sivori, Gopalakrishnan Prakadeeswari, Alexandros Lambropoulos, Michael Coote, Sergei Y. Astakhov, Shahin Yazdani, Dan Milea, Montserrat García, Lydia Álvarez, Kenji Yamashiro, Soumya Raychaudhuri, Pratap Challa, Aparna Rao, Jae H. Kang, Khai Koon Heng, Richard K. Lee, Tien Yin Wong, Alex W. Hewitt, Yoko Ikeda, Kessara Pathanapitoon, Panayiota Founti, Daniella Bach-Holm, Emmanuelle Souzeau, Margaret A. Pericak-Vance, Michèle Ramsay, Nkiru Kizor-Akaraiwe, Yosai Mori, Antonio Maria Fea, Chandrashekaran Shivkumar, Xiao Yu Ng, Jie Jin Wang, Erika Salvi, Giang T T Nguyn, Steffen Uebe, Tamara Zompa, Anne L. Coleman, Werner Zenz, Min Sagong, Luis Fernández-Vega Cueto, Farah Akhtar, Susan Williams, Sarah C. Nelson, Bradford J. Shingleton, Ryuichi Ideta, Leon W. Herndon, Zheng Li, Murat Irkec, M. Roy Wilson, Ewa Kosior-Jarecka, Christian Y. Mardin, Mozhgan Rezaei Kanavi, Tsutomu Ohashi, Abderrahman Rafei, Rengaraj Venkatesh, Stefan Herms, George Chichua, Mohammad Pakravan, Robyn M. Rautenbach, Shi Qi Mok, Trình V Nguyn, Patricio G. Schlottmann, Nassim Khatibi, Daniel Gaston, Masaru Inatani, Morio Ueno, Mukharram M. Bikbov, Eoin Silke, Homa Naderifar, Linda Hansapinyo, Paolo Manunta, Z. Xie, Urszula Lukasik, Eray Atalay, Lulin Huang, Xuyang Liu, Chie Sotozono, Shuang Ru Goh, John H. Fingert, Richard A. Mills, Khaled K. Abu-Amero, Xiao Yin Chen, Matthias Zenkel, Sergo Tabagari, Irma Järvelä, Xueyi Chen, Stéphanie Leruez, Yury S. Astakhov, Sonia Davila, Yildirim Nilgün, Ronnie George, Shin-ichi Manabe, Miguel Coca-Prados, Masahiro Miyake, Ignacio Lischinsky, Rogelio González-Sarmiento, Arkasubhra Ghosh, A. Emelyanov, Çilingir Oguz, Masakazu Nakano, Rohit Shetty, Karen Bedard, Toshiya Sakurai, Yutao Liu, Barbara M Wirostko, Hui Zhang, Ulrich-Christoph Welge-Luessen, Toshiaki Kubota, Vania Castro, Hip X Nguyn, Liyun Jia, Ari Ziskind, Hideki Chuman, Andrew C. Orr, Satoko Nakano, Daniela Paoli, Masahide Yanagi, Aravind Haripriya, Kari Stefansson, Pedro Pablo Rodríguez-Calvo, Hui Meng Soo, Chiea Chuen Khor, Gyulli M. Kazakbaeva, Osvaldo Cuello, Mei Chin Lee, Ki Ho Park, Natalia Porporato, Lourdes de Juan Marcos, Ching-Yu Cheng, Shigeyasu Kazama, Shigeru Kinoshita, Axel M. Hillmer, Alan S. Crandall, Victor H. K. Yong, Ohoud Owaidhah, Rodolfo Perez Grossmann, Jeeyun Ahn, André Reis, Nevbahar Tamçelik, Satoshi Ishiko, Antonio Salas, Ningli Wang, Singapore Eye Research Institute [Singapore] (SERI), Ozaki Eye Hospital [Miyazaki], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), deCODE genetics [Reykjavik], Mizoguchi Eye Hospital [Sasebo], Case Western Reserve University [Cleveland], Aravind Eye Hospital [Madurai, India], University of the Witwatersrand [Johannesburg] (WITS), Pavlov First Saint Petersburg State Medical University [St. Petersburg], Dalhousie University [Halifax], Flinders University [Adelaide, Australia], Kyoto Prefectural University of Medicine [Kyoto, Japon], King Saud University [Riyadh] (KSU), Genome Institute of Singapore (GIS), Aravind Medical Research Foundation (AMRF), Université de Médecine Carol Davila, Harvard Medical School [Boston] (HMS), University of Washington [Seattle], Hayashi Eye Hospital [Fukuoka], Shinjo Eye Clinic [Nagoya], Medical University of Lublin, Inoue Eye Hospital [Tokyo], Hacettepe University = Hacettepe Üniversitesi, Universidad de Oviedo [Oviedo], Kanazawa University (KU), Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Organizacion Medica de Investigacion (OMI BUENOS AIRES), Fundacion para el Estudio del Glaucoma [Buenos Aires], Chercheur indépendant, Eskisehir Osmangazi University, Ufa Eye Research Institute [Bashkortostan], Seoul National University Hospital, Yeungnam University [South Korea], Kyoto University, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Universität Heidelberg [Heidelberg] = Heidelberg University, Birla Institute of Scientific Research (BISR), B. M. Birla Science and Technology Center, Faculty of Computer Science, Department of Pathology and Immunology, Geneva University Hospital (HUG), Key Laboratory for Information System Security, ministry of education, Numerical modeling and high performance computing for evolution problems in complex domains and heterogeneous media (NACHOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (LJAD), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institute of Human Genetics [Erlangen, Allemagne], Department of Ophthalmology, School of Medicine [Thessaloniki, Grèce], Aristotle University of Thessaloniki, Università degli Studi di Siena = University of Siena (UNISI), Department of Medicine, Surgery, and Dentistry, University of Milano, Japan Advanced Institute of Science and Technology (JAIST), Etudes génomiques trans-ethniques des maladies multifactorielles, Kyoto University-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Archaeogenetics Laboratory, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Rheinische Friedrich-Wilhelms-Universität Bonn, University of Kentucky (UK), Helsinki University Eye Hospital, Turku University Hospital, Turku, Finland, COMSATS Institute of Information Technology (CIIT), Department of Epidemiology, Harvard School of Public Health, University of Miami Leonard M. Miller School of Medicine (UMMSM), Brigham and Women's Hospital [Boston], Department of Neuroscience and Pharmacology, Section of Eye Pathology, University of Copenhagen, University of Copenhagen = Københavns Universitet (UCPH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of California [San Diego] (UC San Diego), University of California (UC), University of Iceland [Reykjavik], New York Eye and Ear Infirmary of Mount Sinai [New York] (NYEE), Oita University Faculty of Medicine [Oita, Japon], Radboud University Medical Center [Nijmegen], Oogheelkunde, RS: FHML non-thematic output, Kyoto University [Kyoto], Universidad Nacional Autónoma de México (UNAM), Universität Heidelberg [Heidelberg], Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (JAD), Dipartimento di Scienze oftalmologiche e Neurochirurgiche, Universita' degli Studi di Siena, Siena, Kyoto University [Kyoto]-Institut National de la Santé et de la Recherche Médicale (INSERM), Rothschild Hospital, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Kentucky, University of Copenhagen = Københavns Universitet (KU), University of California, Aung, Tin, Ozaki, Mineo, Lee, Mei Chin, Schlötzer Schrehardt, Ursula, Thorleifsson, Gudmar, Mizoguchi, Takanori, Igo, Robert P, Haripriya, Aravind, Williams, Susan E, Astakhov, Yury S, Orr, Andrew C, Burdon, Kathryn P, Nakano, Satoko, Mori, Kazuhiko, Abu Amero, Khaled, Hauser, Michael, Li, Zheng, Prakadeeswari, Gopalakrishnan, Bailey, Jessica N. Cooke, Cherecheanu, Alina Popa, Kang, Jae H, Nelson, Sarah, Hayashi, Ken, Manabe, Shin Ichi, Kazama, Shigeyasu, Zarnowski, Tomasz, Inoue, Kenji, Irkec, Murat, Coca Prados, Miguel, Sugiyama, Kazuhisa, Järvelä, Irma, Schlottmann, Patricio, Lerner, S. Fabian, Lamari, Hasnaa, Nilgün, Yildirim, Bikbov, Mukharram, Park, Ki Ho, Cha, Soon Cheol, Yamashiro, Kenji, Zenteno, Juan C, Jonas, Jost B, Kumar, Rajesh S, Perera, Shamira A, Chan, Anita S. Y, Kobakhidze, Nino, George, Ronnie, Vijaya, Lingam, Do, Tan, Edward, Deepak P, de Juan Marcos, Lourde, Pakravan, Mohammad, Moghimi, Sasan, Ideta, Ryuichi, Bach Holm, Daniella, Kappelgaard, Per, Wirostko, Barbara, Thomas, Samuel, Gaston, Daniel, Bedard, Karen, Greer, Wenda L, Yang, Zhenglin, Chen, Xueyi, Huang, Lulin, Sang, Jinghong, Jia, Hongyan, Jia, Liyun, Qiao, Chunyan, Zhang, Hui, Liu, Xuyang, Zhao, Bowen, Wang, Ya Xing, Xu, Liang, Leruez, Stéphanie, Reynier, Pascal, Chichua, George, Tabagari, Sergo, Uebe, Steffen, Zenkel, Matthia, Berner, Daniel, Mossböck, Georg, Weisschuh, Nicole, Hoja, Ursula, Welge Luessen, Ulrich Christoph, Mardin, Christian, Founti, Panayiota, Chatzikyriakidou, Anthi, Pappas, Theofani, Anastasopoulos, Eleftherio, Lambropoulos, Alexandro, Ghosh, Arkasubhra, Shetty, Rohit, Porporato, Natalia, Saravanan, Vijayan, Venkatesh, Rengaraj, Shivkumar, Chandrashekaran, Kalpana, Narendran, Sarangapani, Sripriya, Kanavi, Mozhgan R, Beni, Afsaneh Naderi, Yazdani, Shahin, Lashay, Alireza, Naderifar, Homa, Khatibi, Nassim, Fea, Antonio, Lavia, Carlo, Dallorto, Laura, Rolle, Teresa, Frezzotti, Paolo, Paoli, Daniela, Salvi, Erika, Manunta, Paolo, Mori, Yosai, Miyata, Kazunori, Higashide, Tomomi, Chihara, Etsuo, Ishiko, Satoshi, Yoshida, Akitoshi, Yanagi, Masahide, Kiuchi, Yoshiaki, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Aihara, Makoto, Inatani, Masaru, Miyake, Masahiro, Gotoh, Norimoto, Matsuda, Fumihiko, Yoshimura, Nagahisa, Ikeda, Yoko, Ueno, Morio, Sotozono, Chie, Jeoung, Jin Wook, Sagong, Min, Park, Kyu Hyung, Ahn, Jeeyun, Cruz Aguilar, Marisa, Ezzouhairi, Sidi M, Rafei, Abderrahman, Chong, Yaan Fun, Ng, Xiao Yu, Goh, Shuang Ru, Chen, Yueming, Yong, Victor H. K, Khan, Muhammad Imran, Olawoye, Olusola O, Ashaye, Adeyinka O, Ugbede, Idakwo, Onakoya, Adeola, Kizor Akaraiwe, Nkiru, Teekhasaenee, Chaiwat, Suwan, Yanin, Supakontanasan, Wasu, Okeke, Suhanya, Uche, Nkechi J, Asimadu, Ifeoma, Ayub, Humaira, Akhtar, Farah, Kosior Jarecka, Ewa, Lukasik, Urszula, Lischinsky, Ignacio, Castro, Vania, Grossmann, Rodolfo Perez, Megevand, Gordana Sunaric, Roy, Sylvain, Dervan, Edward, Silke, Eoin, Rao, Aparna, Sahay, Priti, Fornero, Pablo, Cuello, Osvaldo, Sivori, Delia, Zompa, Tamara, Mills, Richard A, Souzeau, Emmanuelle, Mitchell, Paul, Wang, Jie Jin, Hewitt, Alex W, Coote, Michael, Crowston, Jonathan G, Astakhov, Sergei Y, Akopov, Eugeny L, Emelyanov, Anton, Vysochinskaya, Vera, Kazakbaeva, Gyulli, Fayzrakhmanov, Rinat, Al Obeidan, Saleh A, Owaidhah, Ohoud, Aljasim, Leyla Ali, Chowbay, Balram, Foo, Jia Nee, Soh, Raphael Q, Sim, Kar Seng, Xie, Zhicheng, Cheong, Augustine W. O, Mok, Shi Qi, Soo, Hui Meng, Chen, Xiao Yin, Peh, Su Qin, Heng, Khai Koon, Husain, Rahat, Ho, Su Ling, Hillmer, Axel M, Cheng, Ching Yu, Escudero Domínguez, Francisco A, González Sarmiento, Rogelio, Martinon Torres, Frederico, Salas, Antonio, Pathanapitoon, Kessara, Hansapinyo, Linda, Wanichwecharugruang, Boonsong, Kitnarong, Nari, Sakuntabhai, Anavaj, Nguyn, Hip X, Nguyn, Giang T. T, Nguyn, Trình V, Zenz, Werner, Binder, Alexander, Klobassa, Daniela S, Hibberd, Martin L, Davila, Sonia, Herms, Stefan, Nöthen, Markus M, Moebus, Susanne, Rautenbach, Robyn M, Ziskind, Ari, Carmichael, Trevor R, Ramsay, Michele, Álvarez, Lydia, García, Montserrat, González Iglesias, Héctor, Rodríguez Calvo, Pedro P, Cueto, Luis Fernández Vega, Oguz, Çilingir, Tamcelik, Nevbahar, Atalay, Eray, Batu, Bilge, Aktas, Dilek, Kasım, Burcu, Wilson, M. Roy, Coleman, Anne L, Liu, Yutao, Challa, Pratap, Herndon, Leon, Kuchtey, Rachel W, Kuchtey, John, Curtin, Karen, Chaya, Craig J, Crandall, Alan, Zangwill, Linda M, Wong, Tien Yin, Nakano, Masakazu, Kinoshita, Shigeru, den Hollander, Anneke I, Vesti, Eija, Fingert, John H, Lee, Richard K, Sit, Arthur J, Shingleton, Bradford J, Wang, Ningli, Cusi, Daniele, Qamar, Raheel, Kraft, Peter, Pericak Vance, Margaret A, Raychaudhuri, Soumya, Heegaard, Steffen, Kivelä, Tero, Reis, André, Kruse, Friedrich E, Weinreb, Robert N, Pasquale, Louis R, Haines, Jonathan L, Thorsteinsdottir, Unnur, Jonasson, Fridbert, Allingham, R. Rand, Milea, Dan, Ritch, Robert, Kubota, Toshiaki, Tashiro, Kei, Vithana, Eranga N, Micheal, Shazia, Topouzis, Foti, Craig, Jamie E, Dubina, Michael, Sundaresan, Periasamy, Stefansson, Kari, Wiggs, Janey L, Pasutto, Francesca, Khor, Chiea Chuen, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and University of Helsinki

Subjects
0301 basic medicine, Male, Calcium Channels/genetics, Messenger, Medizin, PSEUDOEXFOLIATION SYNDROME, Genome-wide association study, BLOOD-PRESSURE, Disease, Exfoliation Syndrome, Eye, Exfoliation Syndrome/ethnology/genetics, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 0302 clinical medicine, PARKINSONS-DISEASE, 80 and over, ta319, Missense mutation, Genetics, Aged, 80 and over, Amino Acid Oxidoreductases/genetics/physiology, Alleles, Amino Acid Oxidoreductases, Amino Acid Substitution, Asian Continental Ancestry Group, Calcium Channels, Cell Adhesion, Extracellular Matrix, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Haplotypes, Humans, Molecular Chaperones, RNA, Messenger, Spheroids, Cellular, Genome-Wide Association Study, Mutation, Missense, Point Mutation, Metaanalysis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, ALZHEIMERS-DISEASE, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Chaperones/biosynthesis/genetics, Biology, SYNONYMOUS MUTATIONS, ta3111, Article, 03 medical and health sciences, Asian People, Asian Continental Ancestry Group/genetics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Allele, Risk factor, GENOME-WIDE ASSOCIATION, Eye/metabolism, Aged, Genetic association, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Haplotype, Individuals, Glaucoma, Odds ratio, Extracellular Matrix/metabolism, RNA, Messenger/biosynthesis, MACULAR DEGENERATION, RISK LOCI, eye diseases, COMMON SEQUENCE VARIANTS, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, 030221 ophthalmology & optometry, RNA, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cellular, Spheroids, Missense, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Polymorphisms, purl.org/pe-repo/ocde/ford#1.06.07 [https], INFLAMMATORY-BOWEL-DISEASE
Abstract

International audience; Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations,and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR= 25, P=2.9 x 10-14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10-8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Published
2017
Full Text
View/download PDF

35. LIST OF CONTRIBUTORS

Author

Acosta, Jorge, Albis-Donado, Oscar, Alencar, Luciana M, Rand Allingham, R, Anand, Nitin, Asota, Ijeoma M, Yu Astakhov, Sergey, Astakhov, Yury S, Babic, Mirko, Baerveldt, George, Bansal, Rajendra K, Barton, Keith, Baudouin, Christophe, Bazzaz, Sheila, Beck, Allen, Bennett, Sonya L, Berke, Stanley J, Berlin, Michael S, Bevin, Tui H, Bloom, Philip A, Bollinger, Kathryn E, Bowd, Christopher, Boyle, John W, IV, Brandt, James D, Broadway, David C, Brocchini, Stephen, Bron, Alain M, Budenz, Donald L, Bull, Natalie D, Bunce, Catey, Burgoyne, Claude F, Buys, Yvonne M, Cantor, Louis B, Caprioli, Joseph, Carassa, Roberto G, Casper, Daniel S, Catoira-Boyle, Yara PM, Ceruti, Piero, Chakrabarti, Debasis, Chakrabarti, Raka (Chatterjee), Challa, Pratap, Chang, Peter T, Chiang, Mark Y-M, Choplin, Neil T, Cioffi, George A, Coleman, Anne L, Congdon, Nathan G, Coote, Michael A, Costa, Vital P, Crabb, David P, Randy Craven, E, Crowston, Jonathan G, Dahan, Elie, Dahlmann-Noor, Annegret H, de Lima, Ricardo, Diamond, Jeremy P, Dorairaj, Syril K, Doshi, Amish, Crawford Downs, J, El Mallah, Mohammed K, ElSayyad, Fathi F, Esson, Douglas W, Fantes, Francisco, Fechter, Herbert P, III, Fechtner, Robert D, Fellman, Ronald L, Fernando, Arosha, Fisher, Ann Caroline, Fitzke, Frederick W, Flammer, Josef, Fortune, Brad, Foster, Paul J, Freedman, Jeffrey, Gandolfi, Stefano A, Garway-Heath, David (Ted), Gazzard, Gus, Gedde, Steven J, Georgoulas, Stelios, Goldberg, Ivan, Graham, Stuart L, Grajewski, Alana, Greenfield, David S, Grehn, Franz, Grigera, Daniel E, Gross, Ronald L, Gupta, Meenakashi, Haefliger, Ivan O, Hafez, Ali S, Hawker, Matthew J, Healey, Paul R, Heatley, Catherine J, Heuer, Dale K, Higginbotham, Eve J, Hitchings, Roger A, Holló, Gábor, Hoste, Ann M, Hylton, Camille, Johnson, Thomas V, Jonas, Jost B, Kahook, Malik Y, Kass, Michael A, Jay Katz, L, Keeffe, Jill E, Tee Khaw, Peng, Khouri, Albert S, Kim, Danny, Klink, Thomas, Konstas, Anastasios GP, Kotecha, Aachal, Krupin, Theodore, Kulkarni, Avinash, Labbé, Antoine, Labbe, Thad, Lacey, Alan, Lam, Dennis SC, Lee, Graham, Lee, Paul P, Lemij, Hans G, Fabian Lerner, S, Lesk, Mark R, Levin, Leonard A, Lewis, Richard A, Lichter, Paul R, Liebmann, Jeffrey M, Sheng Lim, K, Lim, Ridia, Low, Sancy, Mandal, Anil K, Marchini, Giorgio, Martin, Belen, Martin, Keith R, Matchar, David B, McKinley, Steven H, McKinnon, Stuart J, Medeiros, Felipe A, Mermoud, André, Mérula, Rafael V, Meyers, Toni T, Migdal, Clive S, Mikropoulos, Dimitrios G, Minckler, Don, Molteno, Anthony CB, Mora, Paolo, Moreno-Montañés, Javier, Morgan, James E, Muñoz-Negrete, Francisco J, Myers, Jonathan S, Neelakantan, Arvind, Negi, Anil K, Netland, Peter A, Nicolela, Marcelo T, Nofal, Magdy A, Nolan, Winifred, Noureddin, Baha' N, Papadopoulos, Maria, Parikh, Rajul S, Parrish, Richard K, II, Pfeiffer, Norbert, Piltz-Seymour, Jody, Quigley, Harry A, Quinn, Carolyn D, Ramulu, Pradeep Y, Realini, Anthony, Rebolleda, Gema, Reus, Nicolaas J, Reynolds, Adam C, Rhee, Douglas J, Ritch, Robert, Roberts, Cynthia J, Roberts, Michael D, Robin, Alan L, RojanaPongpun, Prin, Roy, Sylvain, Ru, Qian, Salmon, John F, Sampaolesi, Juan Roberto, Sangermani, Chiara, Sarodia, Usman A, Schlötzer-Schrehardt, Ursula, Schnyder, Corinne C, Schultz, Gregory S, Schuman, Joel S, Schwartz, Gail F, Shaarawy, Tarek M, Shah, Peter, Sheets, Clinton W, Sherwood, Mark B, Oto Shiroma, Lineu, Shuba, Lesya M, Singh, Annapurna, Singh, Arun D, Singh, Kuldev, Spaeth, George L, Spratt, Alexander, Stalmans, Ingeborg, Stamper, Robert L, Stewart, William C, Susanna, Remo, Jr, Tamm, Ernst R, Tanna, Angelo P, Teekhasaenee, Chaiwat, Tello, Celso, Tham, Clement CY, Thieme, Hagen, Thomas, Ravi, Thompson, Andrew M, Thulasiraj, Ravilla D, Thygesen, John, Tomey, Karim, Toris, Carol B, Tosi, Roberto, Tsai, James C, Tuli, Sonal S, Tuulonen, Anja, Uhler, Tara A, Ungaro, Nicola, Michael Van Buskirk, E, van Koolwijk, Leonieke ME, Vernon, Stephen A, Vessani, Roberto M, Viswanathan, Ananth C, Weinreb, Robert, Wells, Anthony, Werner, Mark, Wiafe, Boateng, Wilensky, Jacob T, Windisch, Bettina K, Wong, Tina, WuDunn, Darrell, Yip, Jennifer LY, Zangwill, Linda M, Zanutigh, Virginia E, Zeyen, Thierry, and Zimmerman, Thom J

Full Text
View/download PDF

36. LIST OF CONTRIBUTORS

Author

Acosta, Jorge, Albis-Donado, Oscar, Alencar, Luciana M, Rand Allingham, R, Anand, Nitin, Asota, Ijeoma M, Yu Astakhov, Sergey, Astakhov, Yury S, Babic, Mirko, Baerveldt, George, Bansal, Rajendra K, Barton, Keith, Baudouin, Christophe, Bazzaz, Sheila, Beck, Allen, Bennett, Sonya L, Berke, Stanley J, Berlin, Michael S, Bevin, Tui H, Bloom, Philip A, Bollinger, Kathryn E, Bowd, Christopher, Boyle, John W, IV, Brandt, James D, Broadway, David C, Brocchini, Stephen, Bron, Alain M, Budenz, Donald L, Bull, Natalie D, Bunce, Catey, Burgoyne, Claude F, Buys, Yvonne M, Cantor, Louis B, Caprioli, Joseph, Carassa, Roberto G, Casper, Daniel S, Catoira-Boyle, Yara PM, Ceruti, Piero, Chakrabarti, Debasis, Chakrabarti, Raka (Chatterjee), Challa, Pratap, Chang, Peter T, Chiang, Mark Y-M, Choplin, Neil T, Cioffi, George A, Coleman, Anne L, Congdon, Nathan G, Coote, Michael A, Costa, Vital P, Crabb, David P, Randy Craven, E, Crowston, Jonathan G, Dahan, Elie, Dahlmann-Noor, Annegret H, de Lima, Ricardo, Diamond, Jeremy P, Dorairaj, Syril K, Doshi, Amish, Crawford Downs, J, El Mallah, Mohammed K, ElSayyad, Fathi F, Esson, Douglas W, Fantes, Francisco, Fechter, Herbert P, III, Fechtner, Robert D, Fellman, Ronald L, Fernando, Arosha, Fisher, Ann Caroline, Fitzke, Frederick W, Flammer, Josef, Fortune, Brad, Foster, Paul J, Freedman, Jeffrey, Gandolfi, Stefano A, Garway-Heath, David (Ted), Gazzard, Gus, Gedde, Steven J, Georgoulas, Stelios, Goldberg, Ivan, Graham, Stuart L, Grajewski, Alana, Greenfield, David S, Grehn, Franz, Grigera, Daniel E, Gross, Ronald L, Gupta, Meenakashi, Haefliger, Ivan O, Hafez, Ali S, Hawker, Matthew J, Healey, Paul R, Heatley, Catherine J, Heuer, Dale K, Higginbotham, Eve J, Hitchings, Roger A, Holló, Gábor, Hoste, Ann M, Hylton, Camille, Johnson, Thomas V, Jonas, Jost B, Kahook, Malik Y, Kass, Michael A, Jay Katz, L, Keeffe, Jill E, Tee Khaw, Peng, Khouri, Albert S, Kim, Danny, Klink, Thomas, Konstas, Anastasios GP, Kotecha, Aachal, Krupin, Theodore, Kulkarni, Avinash, Labbé, Antoine, Labbe, Thad, Lacey, Alan, Lam, Dennis SC, Lee, Graham, Lee, Paul P, Lemij, Hans G, Fabian Lerner, S, Lesk, Mark R, Levin, Leonard A, Lewis, Richard A, Lichter, Paul R, Liebmann, Jeffrey M, Sheng Lim, K, Lim, Ridia, Low, Sancy, Mandal, Anil K, Marchini, Giorgio, Martin, Belen, Martin, Keith R, Matchar, David B, McKinley, Steven H, McKinnon, Stuart J, Medeiros, Felipe A, Mermoud, André, Mérula, Rafael V, Meyers, Toni T, Migdal, Clive S, Mikropoulos, Dimitrios G, Minckler, Don, Molteno, Anthony CB, Mora, Paolo, Moreno-Montañés, Javier, Morgan, James E, Muñoz-Negrete, Francisco J, Myers, Jonathan S, Neelakantan, Arvind, Negi, Anil K, Netland, Peter A, Nicolela, Marcelo T, Nofal, Magdy A, Nolan, Winifred, Noureddin, Baha' N, Papadopoulos, Maria, Parikh, Rajul S, Parrish, Richard K, II, Pfeiffer, Norbert, Piltz-Seymour, Jody, Quigley, Harry A, Quinn, Carolyn D, Ramulu, Pradeep Y, Realini, Anthony, Rebolleda, Gema, Reus, Nicolaas J, Reynolds, Adam C, Rhee, Douglas J, Ritch, Robert, Roberts, Cynthia J, Roberts, Michael D, Robin, Alan L, RojanaPongpun, Prin, Roy, Sylvain, Ru, Qian, Salmon, John F, Sampaolesi, Juan Roberto, Sangermani, Chiara, Sarodia, Usman A, Schlötzer-Schrehardt, Ursula, Schnyder, Corinne C, Schultz, Gregory S, Schuman, Joel S, Schwartz, Gail F, Shaarawy, Tarek M, Shah, Peter, Sheets, Clinton W, Sherwood, Mark B, Oto Shiroma, Lineu, Shuba, Lesya M, Singh, Annapurna, Singh, Arun D, Singh, Kuldev, Spaeth, George L, Spratt, Alexander, Stalmans, Ingeborg, Stamper, Robert L, Stewart, William C, Susanna, Remo, Jr, Tamm, Ernst R, Tanna, Angelo P, Teekhasaenee, Chaiwat, Tello, Celso, Tham, Clement CY, Thieme, Hagen, Thomas, Ravi, Thompson, Andrew M, Thulasiraj, Ravilla D, Thygesen, John, Tomey, Karim, Toris, Carol B, Tosi, Roberto, Tsai, James C, Tuli, Sonal S, Tuulonen, Anja, Uhler, Tara A, Ungaro, Nicola, Michael Van Buskirk, E, van Koolwijk, Leonieke ME, Vernon, Stephen A, Vessani, Roberto M, Viswanathan, Ananth C, Weinreb, Robert, Wells, Anthony, Werner, Mark, Wiafe, Boateng, Wilensky, Jacob T, Windisch, Bettina K, Wong, Tina, WuDunn, Darrell, Yip, Jennifer LY, Zangwill, Linda M, Zanutigh, Virginia E, Zeyen, Thierry, and Zimmerman, Thom J

Full Text
View/download PDF

37. Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Author

Li Z, Wang Z, Lee MC, Zenkel M, Peh E, Ozaki M, Topouzis F, Nakano S, Chan A, Chen S, Williams SEI, Orr A, Nakano M, Kobakhidze N, Zarnowski T, Popa-Cherecheanu A, Mizoguchi T, Manabe SI, Hayashi K, Kazama S, Inoue K, Mori Y, Miyata K, Sugiyama K, Higashide T, Chihara E, Ideta R, Ishiko S, Yoshida A, Tokumo K, Kiuchi Y, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Aihara M, Inatani M, Mori K, Ikeda Y, Ueno M, Gaston D, Rafuse P, Shuba L, Saunders J, Nicolela M, Chichua G, Tabagari S, Founti P, Sim KS, Meah WY, Soo HM, Chen XY, Chatzikyriakidou A, Keskini C, Pappas T, Anastasopoulos E, Lambropoulos A, Panagiotou ES, Mikropoulos DG, Kosior-Jarecka E, Cheong A, Li Y, Lukasik U, Nongpiur ME, Husain R, Perera SA, Álvarez L, García M, González-Iglesias H, Fernández-Vega Cueto A, Fernández-Vega Cueto L, Martinón-Torres F, Salas A, Oguz Ç, Tamcelik N, Atalay E, Batu B, Irkec M, Aktas D, Kasim B, Astakhov YS, Astakhov SY, Akopov EL, Giessl A, Mardin C, Hellerbrand C, Cooke Bailey JN, Igo RP Jr, Haines JL, Edward DP, Heegaard S, Davila S, Tan P, Kang JH, Pasquale LR, Kruse FE, Reis A, Carmichael TR, Hauser M, Ramsay M, Mossböck G, Yildirim N, Tashiro K, Konstas AGP, Coca-Prados M, Foo JN, Kinoshita S, Sotozono C, Kubota T, Dubina M, Ritch R, Wiggs JL, Pasutto F, Schlötzer-Schrehardt U, Ho YS, Aung T, Tam WL, and Khor CC

Subjects
Aged, Aged, 80 and over, Anterior Chamber pathology, Case-Control Studies, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Female, Humans, Logistic Models, Male, Meta-Analysis as Topic, Middle Aged, RNA, Messenger metabolism, Exome Sequencing, Exfoliation Syndrome genetics, Genetic Variation, Steroid Hydroxylases genetics
Abstract

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness., Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function., Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome., Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function., Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses., Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome., Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results