15 results on '"Wiggs, Janey L."'
Search Results
2. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma
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Bailey, Jessica N Cooke, Loomis, Stephanie J, Kang, Jae H, Allingham, R Rand, Gharahkhani, Puya, Khor, Chiea Chuen, Burdon, Kathryn P, Aschard, Hugues, Chasman, Daniel I, Igo, Robert P, Hysi, Pirro G, Glastonbury, Craig A, Ashley-Koch, Allison, Brilliant, Murray, Brown, Andrew A, Budenz, Donald L, Buil, Alfonso, Cheng, Ching-Yu, Choi, Hyon, Christen, William G, Curhan, Gary, De Vivo, Immaculata, Fingert, John H, Foster, Paul J, Fuchs, Charles, Gaasterland, Douglas, Gaasterland, Terry, Hewitt, Alex W, Hu, Frank, Hunter, David J, Khawaja, Anthony P, Lee, Richard K, Li, Zheng, Lichter, Paul R, Mackey, David A, McGuffin, Peter, Mitchell, Paul, Moroi, Sayoko E, Perera, Shamira A, Pepper, Keating W, Qi, Qibin, Realini, Tony, Richards, Julia E, Ridker, Paul M, Rimm, Eric, Ritch, Robert, Ritchie, Marylyn, Schuman, Joel S, Scott, William K, Singh, Kuldev, Sit, Arthur J, Song, Yeunjoo E, Tamimi, Rulla M, Topouzis, Fotis, Viswanathan, Ananth C, Verma, Shefali Setia, Vollrath, Douglas, Wang, Jie Jin, Weisschuh, Nicole, Wissinger, Bernd, Wollstein, Gadi, Wong, Tien Y, Yaspan, Brian L, Zack, Donald J, Zhang, Kang, Study, EPIC-Norfolk Eye, Weinreb, Robert N, Pericak-Vance, Margaret A, Small, Kerrin, Hammond, Christopher J, Aung, Tin, Liu, Yutao, Vithana, Eranga N, MacGregor, Stuart, Craig, Jamie E, Kraft, Peter, Howell, Gareth, Hauser, Michael A, Pasquale, Louis R, Haines, Jonathan L, and Wiggs, Janey L
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Biological Sciences ,Genetics ,Eye Disease and Disorders of Vision ,Neurodegenerative ,Neurosciences ,Human Genome ,Aging ,Eye ,Ataxin-2 ,Forkhead Transcription Factors ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glaucoma ,Open-Angle ,Humans ,Polymorphism ,Single Nucleotide ,Thioredoxin Reductase 2 ,ANZRAG Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.
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- 2016
3. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma
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Khawaja, Anthony P., Cooke Bailey, Jessica N., Wareham, Nicholas J., Scott, Robert A., Simcoe, Mark, Igo, Jr, Robert P., Song, Yeunjoo E., Wojciechowski, Robert, Cheng, Ching-Yu, Khaw, Peng T., Pasquale, Louis R., Haines, Jonathan L., Foster, Paul J., Wiggs, Janey L., Hammond, Chris J., Hysi, Pirro G., UK Biobank Eye and Vision Consortium, and NEIGHBORHOOD Consortium
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- 2018
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4. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
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Aung, Tin, primary, Ozaki, Mineo, additional, Lee, Mei Chin, additional, Schlötzer-Schrehardt, Ursula, additional, Thorleifsson, Gudmar, additional, Mizoguchi, Takanori, additional, Igo, Robert P, additional, Haripriya, Aravind, additional, Williams, Susan E, additional, Astakhov, Yury S, additional, Orr, Andrew C, additional, Burdon, Kathryn P, additional, Nakano, Satoko, additional, Mori, Kazuhiko, additional, Abu-Amero, Khaled, additional, Hauser, Michael, additional, Li, Zheng, additional, Prakadeeswari, Gopalakrishnan, additional, Bailey, Jessica N Cooke, additional, Cherecheanu, Alina Popa, additional, Kang, Jae H, additional, Nelson, Sarah, additional, Hayashi, Ken, additional, Manabe, Shin-ichi, additional, Kazama, Shigeyasu, additional, Zarnowski, Tomasz, additional, Inoue, Kenji, additional, Irkec, Murat, additional, Coca-Prados, Miguel, additional, Sugiyama, Kazuhisa, additional, Järvelä, Irma, additional, Schlottmann, Patricio, additional, Lerner, S Fabian, additional, Lamari, Hasnaa, additional, Nilgün, Yildirim, additional, Bikbov, Mukharram, additional, Park, Ki Ho, additional, Cha, Soon Cheol, additional, Yamashiro, Kenji, additional, Zenteno, Juan C, additional, Jonas, Jost B, additional, Kumar, Rajesh S, additional, Perera, Shamira A, additional, Chan, Anita S Y, additional, Kobakhidze, Nino, additional, George, Ronnie, additional, Vijaya, Lingam, additional, Do, Tan, additional, Edward, Deepak P, additional, de Juan Marcos, Lourdes, additional, Pakravan, Mohammad, additional, Moghimi, Sasan, additional, Ideta, Ryuichi, additional, Bach-Holm, Daniella, additional, Kappelgaard, Per, additional, Wirostko, Barbara, additional, Thomas, Samuel, additional, Gaston, Daniel, additional, Bedard, Karen, additional, Greer, Wenda L, additional, Yang, Zhenglin, additional, Chen, Xueyi, additional, Huang, Lulin, additional, Sang, Jinghong, additional, Jia, Hongyan, additional, Jia, Liyun, additional, Qiao, Chunyan, additional, Zhang, Hui, additional, Liu, Xuyang, additional, Zhao, Bowen, additional, Wang, Ya-Xing, additional, Xu, Liang, additional, Leruez, Stéphanie, additional, Reynier, Pascal, additional, Chichua, George, additional, Tabagari, Sergo, additional, Uebe, Steffen, additional, Zenkel, Matthias, additional, Berner, Daniel, additional, Mossböck, Georg, additional, Weisschuh, Nicole, additional, Hoja, Ursula, additional, Welge-Luessen, Ulrich-Christoph, additional, Mardin, Christian, additional, Founti, Panayiota, additional, Chatzikyriakidou, Anthi, additional, Pappas, Theofanis, additional, Anastasopoulos, Eleftherios, additional, Lambropoulos, Alexandros, additional, Ghosh, Arkasubhra, additional, Shetty, Rohit, additional, Porporato, Natalia, additional, Saravanan, Vijayan, additional, Venkatesh, Rengaraj, additional, Shivkumar, Chandrashekaran, additional, Kalpana, Narendran, additional, Sarangapani, Sripriya, additional, Kanavi, Mozhgan R, additional, Beni, Afsaneh Naderi, additional, Yazdani, Shahin, additional, lashay, Alireza, additional, Naderifar, Homa, additional, Khatibi, Nassim, additional, Fea, Antonio, additional, Lavia, Carlo, additional, Dallorto, Laura, additional, Rolle, Teresa, additional, Frezzotti, Paolo, additional, Paoli, Daniela, additional, Salvi, Erika, additional, Manunta, Paolo, additional, Mori, Yosai, additional, Miyata, Kazunori, additional, Higashide, Tomomi, additional, Chihara, Etsuo, additional, Ishiko, Satoshi, additional, Yoshida, Akitoshi, additional, Yanagi, Masahide, additional, Kiuchi, Yoshiaki, additional, Ohashi, Tsutomu, additional, Sakurai, Toshiya, additional, Sugimoto, Takako, additional, Chuman, Hideki, additional, Aihara, Makoto, additional, Inatani, Masaru, additional, Miyake, Masahiro, additional, Gotoh, Norimoto, additional, Matsuda, Fumihiko, additional, Yoshimura, Nagahisa, additional, Ikeda, Yoko, additional, Ueno, Morio, additional, Sotozono, Chie, additional, Jeoung, Jin Wook, additional, Sagong, Min, additional, Park, Kyu Hyung, additional, Ahn, Jeeyun, additional, Cruz-Aguilar, Marisa, additional, Ezzouhairi, Sidi M, additional, Rafei, Abderrahman, additional, Chong, Yaan Fun, additional, Ng, Xiao Yu, additional, Goh, Shuang Ru, additional, Chen, Yueming, additional, Yong, Victor H K, additional, Khan, Muhammad Imran, additional, Olawoye, Olusola O, additional, Ashaye, Adeyinka O, additional, Ugbede, Idakwo, additional, Onakoya, Adeola, additional, Kizor-Akaraiwe, Nkiru, additional, Teekhasaenee, Chaiwat, additional, Suwan, Yanin, additional, Supakontanasan, Wasu, additional, Okeke, Suhanya, additional, Uche, Nkechi J, additional, Asimadu, Ifeoma, additional, Ayub, Humaira, additional, Akhtar, Farah, additional, Kosior-Jarecka, Ewa, additional, Lukasik, Urszula, additional, Lischinsky, Ignacio, additional, Castro, Vania, additional, Grossmann, Rodolfo Perez, additional, Megevand, Gordana Sunaric, additional, Roy, Sylvain, additional, Dervan, Edward, additional, Silke, Eoin, additional, Rao, Aparna, additional, Sahay, Priti, additional, Fornero, Pablo, additional, Cuello, Osvaldo, additional, Sivori, Delia, additional, Zompa, Tamara, additional, Mills, Richard A, additional, Souzeau, Emmanuelle, additional, Mitchell, Paul, additional, Wang, Jie Jin, additional, Hewitt, Alex W, additional, Coote, Michael, additional, Crowston, Jonathan G, additional, Astakhov, Sergei Y, additional, Akopov, Eugeny L, additional, Emelyanov, Anton, additional, Vysochinskaya, Vera, additional, Kazakbaeva, Gyulli, additional, Fayzrakhmanov, Rinat, additional, Al-Obeidan, Saleh A, additional, Owaidhah, Ohoud, additional, Aljasim, Leyla Ali, additional, Chowbay, Balram, additional, Foo, Jia Nee, additional, Soh, Raphael Q, additional, Sim, Kar Seng, additional, Xie, Zhicheng, additional, Cheong, Augustine W O, additional, Mok, Shi Qi, additional, Soo, Hui Meng, additional, Chen, Xiao Yin, additional, Peh, Su Qin, additional, Heng, Khai Koon, additional, Husain, Rahat, additional, Ho, Su-Ling, additional, Hillmer, Axel M, additional, Cheng, Ching-Yu, additional, Escudero-Domínguez, Francisco A, additional, González-Sarmiento, Rogelio, additional, Martinon-Torres, Frederico, additional, Salas, Antonio, additional, Pathanapitoon, Kessara, additional, Hansapinyo, Linda, additional, Wanichwecharugruang, Boonsong, additional, Kitnarong, Naris, additional, Sakuntabhai, Anavaj, additional, Nguyn, Hip X, additional, Nguyn, Giang T T, additional, Nguyn, Trình V, additional, Zenz, Werner, additional, Binder, Alexander, additional, Klobassa, Daniela S, additional, Hibberd, Martin L, additional, Davila, Sonia, additional, Herms, Stefan, additional, Nöthen, Markus M, additional, Moebus, Susanne, additional, Rautenbach, Robyn M, additional, Ziskind, Ari, additional, Carmichael, Trevor R, additional, Ramsay, Michele, additional, Álvarez, Lydia, additional, García, Montserrat, additional, González-Iglesias, Héctor, additional, Rodríguez-Calvo, Pedro P, additional, Fernández-Vega Cueto, Luis, additional, Oguz, Çilingir, additional, Tamcelik, Nevbahar, additional, Atalay, Eray, additional, Batu, Bilge, additional, Aktas, Dilek, additional, Kasım, Burcu, additional, Wilson, M Roy, additional, Coleman, Anne L, additional, Liu, Yutao, additional, Challa, Pratap, additional, Herndon, Leon, additional, Kuchtey, Rachel W, additional, Kuchtey, John, additional, Curtin, Karen, additional, Chaya, Craig J, additional, Crandall, Alan, additional, Zangwill, Linda M, additional, Wong, Tien Yin, additional, Nakano, Masakazu, additional, Kinoshita, Shigeru, additional, den Hollander, Anneke I, additional, Vesti, Eija, additional, Fingert, John H, additional, Lee, Richard K, additional, Sit, Arthur J, additional, Shingleton, Bradford J, additional, Wang, Ningli, additional, Cusi, Daniele, additional, Qamar, Raheel, additional, Kraft, Peter, additional, Pericak-Vance, Margaret A, additional, Raychaudhuri, Soumya, additional, Heegaard, Steffen, additional, Kivelä, Tero, additional, Reis, André, additional, Kruse, Friedrich E, additional, Weinreb, Robert N, additional, Pasquale, Louis R, additional, Haines, Jonathan L, additional, Thorsteinsdottir, Unnur, additional, Jonasson, Fridbert, additional, Allingham, R Rand, additional, Milea, Dan, additional, Ritch, Robert, additional, Kubota, Toshiaki, additional, Tashiro, Kei, additional, Vithana, Eranga N, additional, Micheal, Shazia, additional, Topouzis, Fotis, additional, Craig, Jamie E, additional, Dubina, Michael, additional, Sundaresan, Periasamy, additional, Stefansson, Kari, additional, Wiggs, Janey L, additional, Pasutto, Francesca, additional, and Khor, Chiea Chuen, additional
- Published
- 2017
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5. Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression
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Craig, Jamie E., Han, Xikun, Qassim, Ayub, Hassall, Mark, Cooke Bailey, Jessica N., Kinzy, Tyler G., Khawaja, Anthony P., An, Jiyuan, Marshall, Henry, Gharahkhani, Puya, Igo, Robert P., Graham, Stuart L., Healey, Paul R., Ong, Jue-Sheng, Zhou, Tiger, Siggs, Owen, Law, Matthew H., Souzeau, Emmanuelle, Ridge, Bronwyn, Hysi, Pirro G., Burdon, Kathryn P., Mills, Richard A., Landers, John, Ruddle, Jonathan B., Agar, Ashish, Galanopoulos, Anna, White, Andrew J. R., Willoughby, Colin E., Andrew, Nicholas H., Best, Stephen, Vincent, Andrea L., Goldberg, Ivan, Radford-Smith, Graham, Martin, Nicholas G., Montgomery, Grant W., Vitart, Veronique, Hoehn, Rene, Wojciechowski, Robert, Jonas, Jost B., Aung, Tin, Pasquale, Louis R., Cree, Angela Jane, Sivaprasad, Sobha, Vallabh, Neeru A., Viswanathan, Ananth C., Pasutto, Francesca, Haines, Jonathan L., Klaver, Caroline C. W., van Duijn, Cornelia M., Casson, Robert J., Foster, Paul J., Khaw, Peng Tee, Hammond, Christopher J., Mackey, David A., Mitchell, Paul, Lotery, Andrew J., Wiggs, Janey L., Hewitt, Alex W., and MacGregor, Stuart
- Abstract
Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOCvariant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P= 0.004) and surgical intervention in advanced disease (P= 3.6 × 10−6). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.
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- 2020
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6. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome
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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
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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.
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- 2014
7. Detectable clonal mosaicism from birth to old age and its relationship to cancer
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Laurie, Cathy C, primary, Laurie, Cecelia A, additional, Rice, Kenneth, additional, Doheny, Kimberly F, additional, Zelnick, Leila R, additional, McHugh, Caitlin P, additional, Ling, Hua, additional, Hetrick, Kurt N, additional, Pugh, Elizabeth W, additional, Amos, Chris, additional, Wei, Qingyi, additional, Wang, Li-e, additional, Lee, Jeffrey E, additional, Barnes, Kathleen C, additional, Hansel, Nadia N, additional, Mathias, Rasika, additional, Daley, Denise, additional, Beaty, Terri H, additional, Scott, Alan F, additional, Ruczinski, Ingo, additional, Scharpf, Rob B, additional, Bierut, Laura J, additional, Hartz, Sarah M, additional, Landi, Maria Teresa, additional, Freedman, Neal D, additional, Goldin, Lynn R, additional, Ginsburg, David, additional, Li, Jun, additional, Desch, Karl C, additional, Strom, Sara S, additional, Blot, William J, additional, Signorello, Lisa B, additional, Ingles, Sue A, additional, Chanock, Stephen J, additional, Berndt, Sonja I, additional, Le Marchand, Loic, additional, Henderson, Brian E, additional, Monroe, Kristine R, additional, Heit, John A, additional, de Andrade, Mariza, additional, Armasu, Sebastian M, additional, Regnier, Cynthia, additional, Lowe, William L, additional, Hayes, M Geoffrey, additional, Marazita, Mary L, additional, Feingold, Eleanor, additional, Murray, Jeffrey C, additional, Melbye, Mads, additional, Feenstra, Bjarke, additional, Kang, Jae H, additional, Wiggs, Janey L, additional, Jarvik, Gail P, additional, McDavid, Andrew N, additional, Seshan, Venkatraman E, additional, Mirel, Daniel B, additional, Crenshaw, Andrew, additional, Sharopova, Nataliya, additional, Wise, Anastasia, additional, Shen, Jess, additional, Crosslin, David R, additional, Levine, David M, additional, Zheng, Xiuwen, additional, Udren, Jenna I, additional, Bennett, Siiri, additional, Nelson, Sarah C, additional, Gogarten, Stephanie M, additional, Conomos, Matthew P, additional, Heagerty, Patrick, additional, Manolio, Teri, additional, Pasquale, Louis R, additional, Haiman, Christopher A, additional, Caporaso, Neil, additional, and Weir, Bruce S, additional
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- 2012
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8. Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice
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Anderson, Michael G., primary, Smith, Richard S., additional, Hawes, Norman L., additional, Zabaleta, Adriana, additional, Chang, Bo, additional, Wiggs, Janey L., additional, and John, Simon W.M., additional
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- 2001
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9. Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice.
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Anderson, Michael G., Smith, Richard S., Hawes, Norman L., Zabaleta, Adriana, Chang, Bo, Wiggs, Janey L., and John, Simon W.M.
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OPEN-angle glaucoma ,GENETIC mutation ,GENETICS - Abstract
Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (Gpnmb[sup R150X]) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to Gpnmb[sup R150X]; otherwise, similar D2 mice that are not homozygous for Gpnmb[sup R150X] do not develop IPD. ISA is caused by the recessive Tyrp1[sup b] mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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10. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
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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.
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- 2017
11. Corrigendum: a common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
- Author
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Aung T, Ozaki M, Mizoguchi T, Allingham RR, Li Z, Haripriya A, Nakano S, Uebe S, Harder JM, Chan AS, Lee MC, Burdon KP, Astakhov YS, Abu-Amero KK, Zenteno JC, Nilgün Y, Zarnowski T, Pakravan M, Safieh LA, Jia L, Wang YX, Williams S, Paoli D, Schlottmann PG, Huang L, Sim KS, Foo JN, Nakano M, Ikeda Y, Kumar RS, Ueno M, Manabe S, Hayashi K, Kazama S, Ideta R, Mori Y, Miyata K, Sugiyama K, Higashide T, Chihara E, Inoue K, Ishiko S, Yoshida A, Yanagi M, Kiuchi Y, Aihara M, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Matsuda F, Yamashiro K, Gotoh N, Miyake M, Astakhov SY, Osman EA, Al-Obeidan SA, Owaidhah O, Al-Jasim L, Shahwan SA, Fogarty RA, Leo P, Yetkin Y, Oğuz Ç, Kanavi MR, Beni AN, Yazdani S, Akopov EL, Toh KY, Howell GR, Orr AC, Goh Y, Meah WY, Peh SQ, Kosior-Jarecka E, Lukasik U, Krumbiegel M, Vithana EN, Wong TY, Liu Y, Koch AE, Challa P, Rautenbach RM, Mackey DA, Hewitt AW, Mitchell P, Wang JJ, Ziskind A, Carmichael T, Ramakrishnan R, Narendran K, Venkatesh R, Vijayan S, Zhao P, Chen X, Guadarrama-Vallejo D, Cheng CY, Perera SA, Husain R, Ho SL, Welge-Luessen UC, Mardin C, Schloetzer-Schrehardt U, Hillmer AM, Herms S, Moebus S, Nöthen MM, Weisschuh N, Shetty R, Ghosh A, Teo YY, Brown MA, Lischinsky I, Crowston JG, Coote M, Zhao B, Sang J, Zhang N, You Q, Vysochinskaya V, Founti P, Chatzikyriakidou A, Lambropoulos A, Anastasopoulos E, Coleman AL, Wilson MR, Rhee DJ, Kang JH, May-Bolchakova I, Heegaard S, Mori K, Alward WL, Jonas JB, Xu L, Liebmann JM, Chowbay B, Schaeffeler E, Schwab M, Lerner F, Wang N, Yang Z, Frezzotti P, Kinoshita S, Fingert JH, Inatani M, Tashiro K, Reis A, Edward DP, Pasquale LR, Kubota T, Wiggs JL, Pasutto F, Topouzis F, Dubina M, Craig JE, Yoshimura N, Sundaresan P, John SW, Ritch R, Hauser MA, and Khor CC
- Published
- 2015
- Full Text
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12. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
- Author
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Aung T, Ozaki M, Mizoguchi T, Allingham RR, Li Z, Haripriya A, Nakano S, Uebe S, Harder JM, Chan AS, Lee MC, Burdon KP, Astakhov YS, Abu-Amero KK, Zenteno JC, Nilgün Y, Zarnowski T, Pakravan M, Safieh LA, Jia L, Wang YX, Williams S, Paoli D, Schlottmann PG, Huang L, Sim KS, Foo JN, Nakano M, Ikeda Y, Kumar RS, Ueno M, Manabe S, Hayashi K, Kazama S, Ideta R, Mori Y, Miyata K, Sugiyama K, Higashide T, Chihara E, Inoue K, Ishiko S, Yoshida A, Yanagi M, Kiuchi Y, Aihara M, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Matsuda F, Yamashiro K, Gotoh N, Miyake M, Astakhov SY, Osman EA, Al-Obeidan SA, Owaidhah O, Al-Jasim L, Al Shahwan S, Fogarty RA, Leo P, Yetkin Y, Oğuz Ç, Kanavi MR, Beni AN, Yazdani S, Akopov EL, Toh KY, Howell GR, Orr AC, Goh Y, Meah WY, Peh SQ, Kosior-Jarecka E, Lukasik U, Krumbiegel M, Vithana EN, Wong TY, Liu Y, Koch AE, Challa P, Rautenbach RM, Mackey DA, Hewitt AW, Mitchell P, Wang JJ, Ziskind A, Carmichael T, Ramakrishnan R, Narendran K, Venkatesh R, Vijayan S, Zhao P, Chen X, Guadarrama-Vallejo D, Cheng CY, Perera SA, Husain R, Ho SL, Welge-Luessen UC, Mardin C, Schloetzer-Schrehardt U, Hillmer AM, Herms S, Moebus S, Nöthen MM, Weisschuh N, Shetty R, Ghosh A, Teo YY, Brown MA, Lischinsky I, Crowston JG, Coote M, Zhao B, Sang J, Zhang N, You Q, Vysochinskaya V, Founti P, Chatzikyriakidou A, Lambropoulos A, Anastasopoulos E, Coleman AL, Wilson MR, Rhee DJ, Kang JH, May-Bolchakova I, Heegaard S, Mori K, Alward WL, Jonas JB, Xu L, Liebmann JM, Chowbay B, Schaeffeler E, Schwab M, Lerner F, Wang N, Yang Z, Frezzotti P, Kinoshita S, Fingert JH, Inatani M, Tashiro K, Reis A, Edward DP, Pasquale LR, Kubota T, Wiggs JL, Pasutto F, Topouzis F, Dubina M, Craig JE, Yoshimura N, Sundaresan P, John SW, Ritch R, Hauser MA, and Khor CC
- Subjects
- Animals, Asian People genetics, Asian People statistics & numerical data, Case-Control Studies, Chromosome Mapping, Exfoliation Syndrome epidemiology, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle epidemiology, Glaucoma, Open-Angle genetics, HEK293 Cells, HeLa Cells, Humans, Japan epidemiology, MCF-7 Cells, Mice, Mice, Inbred C57BL, Tumor Cells, Cultured, Calcium Channels genetics, Exfoliation Syndrome genetics, Polymorphism, Single Nucleotide
- 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
- Full Text
- View/download PDF
13. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
- Author
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Gharahkhani P, Burdon KP, Fogarty R, Sharma S, Hewitt AW, Martin S, Law MH, Cremin K, Bailey JNC, Loomis SJ, Pasquale LR, Haines JL, Hauser MA, Viswanathan AC, McGuffin P, Topouzis F, Foster PJ, Graham SL, Casson RJ, Chehade M, White AJ, Zhou T, Souzeau E, Landers J, Fitzgerald JT, Klebe S, Ruddle JB, Goldberg I, Healey PR, Mills RA, Wang JJ, Montgomery GW, Martin NG, RadfordSmith G, Whiteman DC, Brown MA, Wiggs JL, Mackey DA, Mitchell P, MacGregor S, and Craig JE
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, Aged, Aged, 80 and over, Australia, Cohort Studies, Female, Gene Expression, Gene Frequency, Genotype, Glaucoma, Open-Angle metabolism, Humans, Immunoblotting, Male, Meta-Analysis as Topic, Microfilament Proteins metabolism, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, United States, ATP Binding Cassette Transporter 1 genetics, Genetic Predisposition to Disease genetics, Glaucoma, Open-Angle genetics, Hydro-Lyases genetics, Microfilament Proteins genetics, Polymorphism, Single Nucleotide
- Abstract
Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.
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- 2014
- Full Text
- View/download PDF
14. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.
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Hysi PG, Cheng CY, Springelkamp H, Macgregor S, Bailey JNC, Wojciechowski R, Vitart V, Nag A, Hewitt AW, Höhn R, Venturini C, Mirshahi A, Ramdas WD, Thorleifsson G, Vithana E, Khor CC, Stefansson AB, Liao J, Haines JL, Amin N, Wang YX, Wild PS, Ozel AB, Li JZ, Fleck BW, Zeller T, Staffieri SE, Teo YY, Cuellar-Partida G, Luo X, Allingham RR, Richards JE, Senft A, Karssen LC, Zheng Y, Bellenguez C, Xu L, Iglesias AI, Wilson JF, Kang JH, van Leeuwen EM, Jonsson V, Thorsteinsdottir U, Despriet DDG, Ennis S, Moroi SE, Martin NG, Jansonius NM, Yazar S, Tai ES, Amouyel P, Kirwan J, van Koolwijk LME, Hauser MA, Jonasson F, Leo P, Loomis SJ, Fogarty R, Rivadeneira F, Kearns L, Lackner KJ, de Jong PTVM, Simpson CL, Pennell CE, Oostra BA, Uitterlinden AG, Saw SM, Lotery AJ, Bailey-Wilson JE, Hofman A, Vingerling JR, Maubaret C, Pfeiffer N, Wolfs RCW, Lemij HG, Young TL, Pasquale LR, Delcourt C, Spector TD, Klaver CCW, Small KS, Burdon KP, Stefansson K, Wong TY, Viswanathan A, Mackey DA, Craig JE, Wiggs JL, van Duijn CM, Hammond CJ, and Aung T
- Subjects
- ABO Blood-Group System genetics, ATP Binding Cassette Transporter 1 genetics, Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 3 genetics, Chromosomes, Human, Pair 9 genetics, Cohort Studies, Female, Fibronectins genetics, Genotype, Glaucoma, Open-Angle genetics, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Glaucoma genetics, Intraocular Pressure genetics
- Abstract
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
- Published
- 2014
- Full Text
- View/download PDF
15. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.
- Author
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Lu Y, Vitart V, Burdon KP, Khor CC, Bykhovskaya Y, Mirshahi A, Hewitt AW, Koehn D, Hysi PG, Ramdas WD, Zeller T, Vithana EN, Cornes BK, Tay WT, Tai ES, Cheng CY, Liu J, Foo JN, Saw SM, Thorleifsson G, Stefansson K, Dimasi DP, Mills RA, Mountain J, Ang W, Hoehn R, Verhoeven VJ, Grus F, Wolfs R, Castagne R, Lackner KJ, Springelkamp H, Yang J, Jonasson F, Leung DY, Chen LJ, Tham CC, Rudan I, Vatavuk Z, Hayward C, Gibson J, Cree AJ, MacLeod A, Ennis S, Polasek O, Campbell H, Wilson JF, Viswanathan AC, Fleck B, Li X, Siscovick D, Taylor KD, Rotter JI, Yazar S, Ulmer M, Li J, Yaspan BL, Ozel AB, Richards JE, Moroi SE, Haines JL, Kang JH, Pasquale LR, Allingham RR, Ashley-Koch A, Mitchell P, Wang JJ, Wright AF, Pennell C, Spector TD, Young TL, Klaver CC, Martin NG, Montgomery GW, Anderson MG, Aung T, Willoughby CE, Wiggs JL, Pang CP, Thorsteinsdottir U, Lotery AJ, Hammond CJ, van Duijn CM, Hauser MA, Rabinowitz YS, Pfeiffer N, Mackey DA, Craig JE, Macgregor S, and Wong TY
- Subjects
- Asian People genetics, Corneal Pachymetry, Forkhead Box Protein O1, Genome-Wide Association Study, Glaucoma genetics, Humans, Microarray Analysis, Odds Ratio, Real-Time Polymerase Chain Reaction, White People genetics, Cornea anatomy & histology, Fibronectins genetics, Forkhead Transcription Factors genetics, Genetic Loci genetics, Keratoconus genetics
- Abstract
Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.
- Published
- 2013
- Full Text
- View/download PDF
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