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

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

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Zheng Li
Aung et al., 2015

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Nature Research, Nature Genetics, 4(47), p. 387-392, 2015

DOI: 10.1038/ng.3226

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@article{Aung2015,
  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.},
  author = {Aung, Tin and Rand Allingham, R. and Ozaki, Mineo and Nakano, Satoko and Zenteno, Juan C. and Zarnowski, Tomasz and Mizoguchi, Takanori and Nilgün, Yildirim and Pakravan, Mohammad and Safieh, Leen Abu and Wang, Ya Xing and Li, Zheng and Williams, Susan and Nilguen, Yildirim and Paoli, Daniela and Schlottmann, Patricio G. and Sim, Kar Seng and Nakano, Masakazu and Ueno, Morio and Manabe, Shin-Ichi and Uebe, Steffen and Mori, Yosai and Miyata, Kazunori and Sugiyama, Kazuhisa and Yoshida, Akitoshi and Yanagi, Masahide and Ohashi, Tsutomu and Ouz, Çilingir and Sakurai, Toshiya and Oğuz, Çilingir and Sugimoto, Takako and Matsuda, Fumihiko and Nakano, S. and Yamashiro, Kenji and Haripriya, Aravind and Miyake, Masahiro and Rr, Allingham and Osman, Essam A. and Ziskind, Ari and Owaidhah, Ohoud and Shahwan, Sami Al and Allingham, R. Rand and Oguz, Cilingir and Leo, Paul and Zhao, Peiquan and Yetkin, Yaz and Harder, Jeffrey M. and Chan, Anita S. Y. and Burdon, Kathryn P. and Yazdani, Shahin and Astakhov, Yury S. and Toh, Kai-Yee and Abu Amero, Khaled K. and Orr, Andrew C. and Meah, Wee Yang and Peh, Su Qin and Jia, Liyun and Lukasik, Urszula and Zhao, Bowen and Huang, Lulin and Vithana, Eranga N. and Zhang, Nihong and Wong, Tien Yin and Foo, Jia Nee and Liu, Yutao and Ouz, C. and Ikeda, Yoko and Kumar, Rajesh S. and Rautenbach, Robyn M. and Mackey, David A. and Hayashi, Ken and Noethen, Markus M. and Kazama, Shigeyasu and Mitchell, Paul and Wang, Jie Jin and Ideta, Ryuichi and Lee, Mei Chin and Ramakrishnan, Rangappa and Roy Wilson, M. and Narendran, Kalpana and Higashide, Tomomi and Venkatesh, Rangaraj and Chihara, Etsuo and Vijayan, Saravanan and Inoue, Kenji and Ishiko, Satoshi and Perera, Shamira A. and Kiuchi, Yoshiaki and Aihara, Makoto and Welge-Luessen, Ulrich-Christoph and Mardin, Christian and Chuman, Hideki and Schloetzer-Schrehardt, Ursula and Gotoh, Norimoto and Moebus, Susanne and Nöthen, Markus M. and Astakhov, Sergei Y. and Weisschuh, Nicole and Al-Obeidan, Saleh A. and Shetty, Rohit and Al-Jasim, Leyla and Teo, Yik Ying and Fogarty, Rhys A. and Lischinsky, Ignacio and Palmer, Colin and Sang, Jinghong and Kanavi, Mozhgan Rezaei and Beni, Afsaneh Nederi and You, Qisheng and Vysochinskaya, Vera and Akopov, Evgeny L. and Jm, Harder and Howell, Gareth R. and Goh, Yufen and Wilson, M. Roy and Abu-Amero, Khaled K. and Rhee, Douglas J. and Kosior-Jarecka, Ewa and May-Bolchakova, Inna and Krumbiegel, Mandy and Mori, Kazuhiko and Koch, Allison E. Ashley and Abu Safieh, Leen and Challa, Pratap and Xu, Liang and Liebmann, Jeffrey M. and As, Chan and Hewitt, Alex W. and Schaeffeler, Elke and Schwab, Matthias and Lerner, Fabian and Carmichael, Trevor and Wang, Ningli and Yang, Zhenglin and Chen, Xueyi and Tashiro, Kei and Guadarrama-Vallejo, Dalia and Reis, André and Cheng, Ching Yu and Pasquale, Louis R. and Husain, Rahat and Mc, Lee and Ho, Su-Ling and Wiggs, Janey L. and Pasutto, Francesca and Topouzis, Fotis and Hillmer, Axel M. and Herms, Stefan and Yoshimura, Nagahisa and Al Shahwan, Sami and Sundaresan, Periasamy and Ghosh, Arkasubhra and Ritch, Robert and Brown, Matthew A. and Crowston, Jonathan G. and Kp, Burdon and Coote, Michael and Ashley Koch, Allison E. and Founti, Panayiota and Chatzikyriakidou, Anthoula and Lambropoulos, Alexandros and Anastasopoulos, Eleftherios and Coleman, Anne L. and Kang, Jae Hee and Heegaard, Steffen and Ys, Astakhov and Alward, Wallace L. M. and Jonas, Jost B. and Chowbay, Balram and Frezzotti, Paolo and Kinoshita, Shigeru and Fingert, John H. and Kk, Abu Amero and Inatani, Masaru and Edward, Deepak P. and Kubota, Toshiaki and Dubina, Michael and Craig, Jamie E. and John, Simon W. M. and Hauser, Michael A. and Cc, Khor and Khor, Chiea-Chuen},
  doi = {10.1038/ng.3226},
  journal = {Nature Genetics},
  month = {feb},
  pages = {387-392},
  title = {A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome},
  url = {http://www.nature.com/articles/ng.3226.pdf},
  volume = {47},
  year = {2015}
}

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

Journal article published in 2015 by Tin Aung, R. Rand Allingham, Mineo Ozaki, Satoko Nakano, Juan C. Zenteno, Tomasz Zarnowski, Takanori Mizoguchi, Yildirim Nilgün, Mohammad Pakravan, Leen Abu Safieh, Ya Xing Wang, Zheng Li

, Susan Williams

, Yildirim Nilguen, Daniela Paoli and other authors. Tin Aung, R. Rand Allingham, Mineo Ozaki, Satoko Nakano, Juan C. Zenteno, Tomasz Zarnowski, Takanori Mizoguchi, Yildirim Nilgün, Mohammad Pakravan, Leen Abu Safieh, Ya Xing Wang, Zheng Li

, Susan Williams

, Yildirim Nilguen, Daniela Paoli, Patricio G. Schlottmann, Kar Seng Sim

, Masakazu Nakano, Morio Ueno, Shin-Ichi Manabe, Steffen Uebe, Yosai Mori, Kazunori Miyata, Kazuhisa Sugiyama, Akitoshi Yoshida, Masahide Yanagi, Tsutomu Ohashi, Çilingir Ouz, Toshiya Sakurai, Çilingir Oğuz, Takako Sugimoto, Fumihiko Matsuda, S. Nakano, Kenji Yamashiro

, Aravind Haripriya, Masahiro Miyake, Allingham Rr, Essam A. Osman, Ari Ziskind, Ohoud Owaidhah, Sami Al Shahwan, R. Rand Allingham, Cilingir Oguz, Paul Leo, Peiquan Zhao, Yaz Yetkin, Jeffrey M. Harder, Anita S. Y. Chan, Kathryn P. Burdon

, Shahin Yazdani, Yury S. Astakhov, Kai-Yee Toh, Khaled K. Abu Amero, Andrew C. Orr, Wee Yang Meah, Su Qin Peh, Liyun Jia, Urszula Lukasik, Bowen Zhao, Lulin Huang, Eranga N. Vithana, Nihong Zhang, Tien Yin Wong, Jia Nee Foo

, Yutao Liu, C. Ouz, Yoko Ikeda, Rajesh S. Kumar, Robyn M. Rautenbach, David A. Mackey, Ken Hayashi, Markus M. Noethen, Shigeyasu Kazama, Paul Mitchell, Jie Jin Wang, Ryuichi Ideta, Mei Chin Lee

, Rangappa Ramakrishnan, M. Roy Wilson, Kalpana Narendran, Tomomi Higashide, Rangaraj Venkatesh, Etsuo Chihara, Saravanan Vijayan, Kenji Inoue, Satoshi Ishiko, Shamira A. Perera, Yoshiaki Kiuchi, Makoto Aihara, Ulrich-Christoph Welge-Luessen, Christian Mardin, Hideki Chuman, Ursula Schloetzer-Schrehardt, Norimoto Gotoh, Susanne Moebus, Markus M. Nöthen, Sergei Y. Astakhov, Nicole Weisschuh, Saleh A. Al-Obeidan, Rohit Shetty, Leyla Al-Jasim, Yik Ying Teo, Rhys A. Fogarty, Ignacio Lischinsky, Colin Palmer, Jinghong Sang, Mozhgan Rezaei Kanavi, Afsaneh Nederi Beni, Qisheng You

, Vera Vysochinskaya, Evgeny L. Akopov, Harder Jm, Gareth R. Howell, Yufen Goh, M. Roy Wilson, Khaled K. Abu-Amero, Douglas J. Rhee, Ewa Kosior-Jarecka, Inna May-Bolchakova, Mandy Krumbiegel, Kazuhiko Mori, Allison E. Ashley Koch, Leen Abu Safieh, Pratap Challa, Liang Xu, Jeffrey M. Liebmann, Chan As, Alex W. Hewitt, Elke Schaeffeler, Matthias Schwab, Fabian Lerner, Trevor Carmichael, Ningli Wang, Zhenglin Yang, Xueyi Chen, Kei Tashiro, Dalia Guadarrama-Vallejo, André Reis

, Ching Yu Cheng

, Louis R. Pasquale, Rahat Husain, Lee Mc, Su-Ling Ho, Janey L. Wiggs, Francesca Pasutto, Fotis Topouzis, Axel M. Hillmer, Stefan Herms, Nagahisa Yoshimura, Sami Al Shahwan, Periasamy Sundaresan, Arkasubhra Ghosh, Robert Ritch, Matthew A. Brown, Jonathan G. Crowston, Burdon Kp, Michael Coote, Allison E. Ashley Koch, Panayiota Founti, Anthoula Chatzikyriakidou, Alexandros Lambropoulos, Eleftherios Anastasopoulos, Anne L. Coleman, Jae Hee Kang, Steffen Heegaard, Astakhov Ys, Wallace L. M. Alward, Jost B. Jonas

, Balram Chowbay, Paolo Frezzotti, Shigeru Kinoshita, John H. Fingert, Abu Amero Kk, Masaru Inatani, Deepak P. Edward, Toshiaki Kubota, Michael Dubina, Jamie E. Craig, Simon W. M. John, Michael A. Hauser, Khor Cc, Chiea-Chuen Khor

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

Abstract