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

Tin Aung, Mineo Ozaki, Mei Chin Lee, Ursula Schlötzer-Schrehardt, Gudmar Thorleifsson, Takanori Mizoguchi, Robert P. Igo, Aravind Haripriya, Susan E. Williams, Yury S. Astakhov, Andrew C. Orr, Kathryn P. Burdon, Satoko Nakano, Kazuhiko Mori, Khaled Abu-Amero, Michael Hauser, Zheng Li, Gopalakrishnan Prakadeeswari, Jessica N.Cooke Bailey, Alina Popa Cherecheanu & 269 others Jae H. Kang, Sarah Nelson, Ken Hayashi, Shin Ichi Manabe, Shigeyasu Kazama, Tomasz Zarnowski, Kenji Inoue, Murat Irkec, Miguel Coca-Prados, Kazuhisa Sugiyama, Irma Järvelä, Patricio Schlottmann, S. Fabian Lerner, Hasnaa Lamari, Yildirim Nilgün, Mukharram Bikbov, Ki Ho Park, Soon Cheol Cha, Kenji Yamashiro, Juan C. Zenteno, Jost B. Jonas, Rajesh S. Kumar, Shamira A. Perera, Anita S.Y. Chan, Nino Kobakhidze, Ronnie George, Lingam Vijaya, Tan Do, Deepak P. Edward, Lourdes De Juan Marcos, Mohammad Pakravan, Sasan Moghimi, Ryuichi Ideta, Daniella Bach-Holm, Per Kappelgaard, Barbara Wirostko, Samuel Thomas, Daniel Gaston, Karen Bedard, Wenda L. Greer, Zhenglin Yang, Xueyi Chen, Lulin Huang, Jinghong Sang, Hongyan Jia, Liyun Jia, Chunyan Qiao, Hui Zhang, Xuyang Liu, Bowen Zhao, Ya Xing Wang, Liang Xu, Stéphanie Leruez, Pascal Reynier, George Chichua, Sergo Tabagari, Steffen Uebe, Matthias Zenkel, Daniel Berner, Georg Mossböck, Nicole Weisschuh, Ursula Hoja, Ulrich Christoph Welge-Luessen, Christian Mardin, Panayiota Founti, Anthi Chatzikyriakidou, Theofanis Pappas, Eleftherios Anastasopoulos, Alexandros Lambropoulos, Arkasubhra Ghosh, Rohit Shetty, Natalia Porporato, Vijayan Saravanan, Rengaraj Venkatesh, Chandrashekaran Shivkumar, Narendran Kalpana, Sripriya Sarangapani, Mozhgan R. Kanavi, Afsaneh Naderi Beni, Shahin Yazdani, Alireza Lashay, Homa Naderifar, Nassim Khatibi, Antonio Fea, Carlo Lavia, Laura Dallorto, Teresa Rolle, Paolo Frezzotti, Daniela Paoli, Erika Salvi, Paolo Manunta, Yosai Mori, Kazunori Miyata, Tomomi Higashide, Etsuo Chihara, Satoshi Ishiko, Akitoshi Yoshida, Masahide Yanagi, Yoshiaki Kiuchi, Tsutomu Ohashi, Toshiya Sakurai, Takako Sugimoto, Hideki Chuman, Makoto Aihara, Masaru Inatani, Masahiro Miyake, Norimoto Gotoh, Fumihiko Matsuda, Nagahisa Yoshimura, Yoko Ikeda, Morio Ueno, Chie Sotozono, Jin Wook Jeoung, Min Sagong, Kyu Hyung Park, Jeeyun Ahn, Marisa Cruz-Aguilar, Sidi M. Ezzouhairi, Abderrahman Rafei, Yaan Fun Chong, Xiao Yu Ng, Shuang Ru Goh, Yueming Chen, Victor H.K. Yong, Muhammad Imran Khan, Olusola O. Olawoye, Adeyinka O. Ashaye, Idakwo Ugbede, Adeola Onakoya, Nkiru Kizor-Akaraiwe, Chaiwat Teekhasaenee, Yanin Suwan, Wasu Supakontanasan, Suhanya Okeke, Nkechi J. Uche, Ifeoma Asimadu, Humaira Ayub, Farah Akhtar, Ewa Kosior-Jarecka, Urszula Lukasik, Ignacio Lischinsky, Vania Castro, Rodolfo Perez Grossmann, Gordana Sunaric Megevand, Sylvain Roy, Edward Dervan, Eoin Silke, Aparna Rao, Priti Sahay, Pablo Fornero, Osvaldo Cuello, Delia Sivori, Tamara Zompa, Richard A. Mills, Emmanuelle Souzeau, Paul Mitchell, Jie Jin Wang, Alex W. Hewitt, Michael Coote, Jonathan G. Crowston, Sergei Y. Astakhov, Eugeny L. Akopov, Anton Emelyanov, Vera Vysochinskaya, Gyulli Kazakbaeva, Rinat Fayzrakhmanov, Saleh A. Al-Obeidan, Ohoud Owaidhah, Leyla Ali Aljasim, Balram Chowbay, Jia Nee Foo, Raphael Q. Soh, Kar Seng Sim, Zhicheng Xie, Augustine W.O. Cheong, Shi Qi Mok, Hui Meng Soo, Xiao Yin Chen, Su Qin Peh, Khai Koon Heng, Rahat Husain, Su Ling Ho, Axel M. Hillmer, Ching Yu Cheng, Francisco A. Escudero-Domínguez, Rogelio González-Sarmiento, Frederico Martinon-Torres, Antonio Salas, Kessara Pathanapitoon, Linda Hansapinyo, Boonsong Wanichwecharugruang, Naris Kitnarong, Anavaj Sakuntabhai, Hip X. Nguyn, Giang T.T. Nguyn, Trình V. Nguyn, Werner Zenz, Alexander Binder, Daniela S. Klobassa, Martin L. Hibberd, Sonia Davila, Stefan Herms, Markus M. Nöthen, Susanne Moebus, Robyn M. Rautenbach, Ari Ziskind, Trevor R. Carmichael, Michele Ramsay, Lydia Álvarez, Montserrat García, Héctor González-Iglesias, Pedro P. Rodríguez-Calvo, Luis Fernández Vega Cueto, Çilingir Oguz, Nevbahar Tamcelik, Eray Atalay, Bilge Batu, Dilek Aktas, Burcu Kaslm, M. Roy Wilson, Anne L. Coleman, Yutao Liu, Pratap Challa, Leon Herndon, Rachel W. Kuchtey, John Kuchtey, Karen Curtin, Craig J. Chaya, Alan Crandall, Linda M. Zangwill, Tien Yin Wong, Masakazu Nakano, Shigeru Kinoshita, Anneke I. Den Hollander, Eija Vesti, John H. Fingert, Richard K. Lee, Arthur J. Sit, Bradford J. Shingleton, Ningli Wang, Daniele Cusi, Raheel Qamar, Peter Kraft, Margaret A. Pericak-Vance, Soumya Raychaudhuri, Steffen Heegaard, Tero Kivelä, André Reis, Friedrich E. Kruse, Robert N. Weinreb, Louis R. Pasquale, Jonathan L. Haines, Unnur Thorsteinsdottir, Fridbert Jonasson, R. Rand Allingham, Dan Milea, Robert Ritch, Toshiaki Kubota, Kei Tashiro, Eranga N. Vithana, Shazia Micheal, Fotis Topouzis, Jamie E. Craig, Michael Dubina, Periasamy Sundaresan, Kari Stefansson, Janey L. Wiggs, Francesca Pasutto, Chiea Chuen Khor

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)993-1004
Number of pages12
JournalNature Genetics
Volume49
Issue number7
DOIs
StatePublished - Jul 1 2017

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Exfoliation Syndrome
Genome-Wide Association Study
Genetic Association Studies
Blindness
Glaucoma
Alleles
Odds Ratio
Genome
Pathology
Population
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Aung, T., Ozaki, M., Lee, M. C., Schlötzer-Schrehardt, U., Thorleifsson, G., Mizoguchi, T., ... Khor, C. C. (2017). Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nature Genetics, 49(7), 993-1004. https://doi.org/10.1038/ng.3875

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. / 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, 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; 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, Naris; 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; Kaslm, 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, Fotis; Craig, Jamie E.; Dubina, Michael; Sundaresan, Periasamy; Stefansson, Kari; Wiggs, Janey L.; Pasutto, Francesca; Khor, Chiea Chuen.

In: Nature Genetics, Vol. 49, No. 7, 01.07.2017, p. 993-1004.

Research output: Contribution to journalArticle

Aung, T, Ozaki, M, Lee, MC, Schlötzer-Schrehardt, U, Thorleifsson, G, Mizoguchi, T, Igo, RP, Haripriya, A, Williams, SE, Astakhov, YS, Orr, AC, Burdon, KP, Nakano, S, Mori, K, Abu-Amero, K, Hauser, M, Li, Z, Prakadeeswari, G, Bailey, JNC, Cherecheanu, AP, Kang, JH, Nelson, S, Hayashi, K, Manabe, SI, Kazama, S, Zarnowski, T, Inoue, K, Irkec, M, Coca-Prados, M, Sugiyama, K, Järvelä, I, Schlottmann, P, Lerner, SF, Lamari, H, Nilgün, Y, Bikbov, M, Park, KH, Cha, SC, Yamashiro, K, Zenteno, JC, Jonas, JB, Kumar, RS, Perera, SA, Chan, ASY, Kobakhidze, N, George, R, Vijaya, L, Do, T, Edward, DP, De Juan Marcos, L, Pakravan, M, Moghimi, S, Ideta, R, Bach-Holm, D, Kappelgaard, P, Wirostko, B, Thomas, S, Gaston, D, Bedard, K, Greer, WL, Yang, Z, Chen, X, Huang, L, Sang, J, Jia, H, Jia, L, Qiao, C, Zhang, H, Liu, X, Zhao, B, Wang, YX, Xu, L, Leruez, S, Reynier, P, Chichua, G, Tabagari, S, Uebe, S, Zenkel, M, Berner, D, Mossböck, G, Weisschuh, N, Hoja, U, Welge-Luessen, UC, Mardin, C, Founti, P, Chatzikyriakidou, A, Pappas, T, Anastasopoulos, E, Lambropoulos, A, Ghosh, A, Shetty, R, Porporato, N, Saravanan, V, Venkatesh, R, Shivkumar, C, Kalpana, N, Sarangapani, S, Kanavi, MR, Beni, AN, Yazdani, S, Lashay, A, Naderifar, H, Khatibi, N, Fea, A, Lavia, C, Dallorto, L, Rolle, T, Frezzotti, P, Paoli, D, Salvi, E, Manunta, P, Mori, Y, Miyata, K, Higashide, T, Chihara, E, Ishiko, S, Yoshida, A, Yanagi, M, Kiuchi, Y, Ohashi, T, Sakurai, T, Sugimoto, T, Chuman, H, Aihara, M, Inatani, M, Miyake, M, Gotoh, N, Matsuda, F, Yoshimura, N, Ikeda, Y, Ueno, M, Sotozono, C, Jeoung, JW, Sagong, M, Park, KH, Ahn, J, Cruz-Aguilar, M, Ezzouhairi, SM, Rafei, A, Chong, YF, Ng, XY, Goh, SR, Chen, Y, Yong, VHK, Khan, MI, Olawoye, OO, Ashaye, AO, Ugbede, I, Onakoya, A, Kizor-Akaraiwe, N, Teekhasaenee, C, Suwan, Y, Supakontanasan, W, Okeke, S, Uche, NJ, Asimadu, I, Ayub, H, Akhtar, F, Kosior-Jarecka, E, Lukasik, U, Lischinsky, I, Castro, V, Grossmann, RP, Megevand, GS, Roy, S, Dervan, E, Silke, E, Rao, A, Sahay, P, Fornero, P, Cuello, O, Sivori, D, Zompa, T, Mills, RA, Souzeau, E, Mitchell, P, Wang, JJ, Hewitt, AW, Coote, M, Crowston, JG, Astakhov, SY, Akopov, EL, Emelyanov, A, Vysochinskaya, V, Kazakbaeva, G, Fayzrakhmanov, R, Al-Obeidan, SA, Owaidhah, O, Aljasim, LA, Chowbay, B, Foo, JN, Soh, RQ, Sim, KS, Xie, Z, Cheong, AWO, Mok, SQ, Soo, HM, Chen, XY, Peh, SQ, Heng, KK, Husain, R, Ho, SL, Hillmer, AM, Cheng, CY, Escudero-Domínguez, FA, González-Sarmiento, R, Martinon-Torres, F, Salas, A, Pathanapitoon, K, Hansapinyo, L, Wanichwecharugruang, B, Kitnarong, N, Sakuntabhai, A, Nguyn, HX, Nguyn, GTT, Nguyn, TV, Zenz, W, Binder, A, Klobassa, DS, Hibberd, ML, Davila, S, Herms, S, Nöthen, MM, Moebus, S, Rautenbach, RM, Ziskind, A, Carmichael, TR, Ramsay, M, Álvarez, L, García, M, González-Iglesias, H, Rodríguez-Calvo, PP, Cueto, LFV, Oguz, Ç, Tamcelik, N, Atalay, E, Batu, B, Aktas, D, Kaslm, B, Wilson, MR, Coleman, AL, Liu, Y, Challa, P, Herndon, L, Kuchtey, RW, Kuchtey, J, Curtin, K, Chaya, CJ, Crandall, A, Zangwill, LM, Wong, TY, Nakano, M, Kinoshita, S, Den Hollander, AI, Vesti, E, Fingert, JH, Lee, RK, Sit, AJ, Shingleton, BJ, Wang, N, Cusi, D, Qamar, R, Kraft, P, Pericak-Vance, MA, Raychaudhuri, S, Heegaard, S, Kivelä, T, Reis, A, Kruse, FE, Weinreb, RN, Pasquale, LR, Haines, JL, Thorsteinsdottir, U, Jonasson, F, Allingham, RR, Milea, D, Ritch, R, Kubota, T, Tashiro, K, Vithana, EN, Micheal, S, Topouzis, F, Craig, JE, Dubina, M, Sundaresan, P, Stefansson, K, Wiggs, JL, Pasutto, F & Khor, CC 2017, 'Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci', Nature Genetics, vol. 49, no. 7, pp. 993-1004. https://doi.org/10.1038/ng.3875
Aung T, Ozaki M, Lee MC, Schlötzer-Schrehardt U, Thorleifsson G, Mizoguchi T et al. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nature Genetics. 2017 Jul 1;49(7):993-1004. https://doi.org/10.1038/ng.3875
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, 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 ; 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, Naris ; 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 ; Kaslm, 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, Fotis ; Craig, Jamie E. ; Dubina, Michael ; Sundaresan, Periasamy ; Stefansson, Kari ; Wiggs, Janey L. ; Pasutto, Francesca ; Khor, Chiea Chuen. / Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. In: Nature Genetics. 2017 ; Vol. 49, No. 7. pp. 993-1004.
@article{2c47a799253d49d59781f16a7178d971,
title = "Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci",
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.",
author = "Tin Aung and Mineo Ozaki and Lee, {Mei Chin} and Ursula Schl{\"o}tzer-Schrehardt and Gudmar Thorleifsson and Takanori Mizoguchi and Igo, {Robert P.} and Aravind Haripriya and Williams, {Susan E.} and Astakhov, {Yury S.} and Orr, {Andrew C.} and Burdon, {Kathryn P.} and Satoko Nakano and Kazuhiko Mori and Khaled Abu-Amero and Michael Hauser and Zheng Li and Gopalakrishnan Prakadeeswari and Bailey, {Jessica N.Cooke} and Cherecheanu, {Alina Popa} and Kang, {Jae H.} and Sarah Nelson and Ken Hayashi and Manabe, {Shin Ichi} and Shigeyasu Kazama and Tomasz Zarnowski and Kenji Inoue and Murat Irkec and Miguel Coca-Prados and Kazuhisa Sugiyama and Irma J{\"a}rvel{\"a} and Patricio Schlottmann and Lerner, {S. Fabian} and Hasnaa Lamari and Yildirim Nilg{\"u}n and Mukharram Bikbov and Park, {Ki Ho} and Cha, {Soon Cheol} and Kenji Yamashiro and Zenteno, {Juan C.} and Jonas, {Jost B.} and Kumar, {Rajesh S.} and Perera, {Shamira A.} and Chan, {Anita S.Y.} and Nino Kobakhidze and Ronnie George and Lingam Vijaya and Tan Do and Edward, {Deepak P.} and {De Juan Marcos}, Lourdes and Mohammad Pakravan and Sasan Moghimi and Ryuichi Ideta and Daniella Bach-Holm and Per Kappelgaard and Barbara Wirostko and Samuel Thomas and Daniel Gaston and Karen Bedard and Greer, {Wenda L.} and Zhenglin Yang and Xueyi Chen and Lulin Huang and Jinghong Sang and Hongyan Jia and Liyun Jia and Chunyan Qiao and Hui Zhang and Xuyang Liu and Bowen Zhao and Wang, {Ya Xing} and Liang Xu and St{\'e}phanie Leruez and Pascal Reynier and George Chichua and Sergo Tabagari and Steffen Uebe and Matthias Zenkel and Daniel Berner and Georg Mossb{\"o}ck and Nicole Weisschuh and Ursula Hoja and Welge-Luessen, {Ulrich Christoph} and Christian Mardin and Panayiota Founti and Anthi Chatzikyriakidou and Theofanis Pappas and Eleftherios Anastasopoulos and Alexandros Lambropoulos and Arkasubhra Ghosh and Rohit Shetty and Natalia Porporato and Vijayan Saravanan and Rengaraj Venkatesh and Chandrashekaran Shivkumar and Narendran Kalpana and Sripriya Sarangapani and Kanavi, {Mozhgan R.} and Beni, {Afsaneh Naderi} and Shahin Yazdani and Alireza Lashay and Homa Naderifar and Nassim Khatibi and Antonio Fea and Carlo Lavia and Laura Dallorto and Teresa Rolle and Paolo Frezzotti and Daniela Paoli and Erika Salvi and Paolo Manunta and Yosai Mori and Kazunori Miyata and Tomomi Higashide and Etsuo Chihara and Satoshi Ishiko and Akitoshi Yoshida and Masahide Yanagi and Yoshiaki Kiuchi and Tsutomu Ohashi and Toshiya Sakurai and Takako Sugimoto and Hideki Chuman and Makoto Aihara and Masaru Inatani and Masahiro Miyake and Norimoto Gotoh and Fumihiko Matsuda and Nagahisa Yoshimura and Yoko Ikeda and Morio Ueno and Chie Sotozono and Jeoung, {Jin Wook} and Min Sagong and Park, {Kyu Hyung} and Jeeyun Ahn and Marisa Cruz-Aguilar and Ezzouhairi, {Sidi M.} and Abderrahman Rafei and Chong, {Yaan Fun} and Ng, {Xiao Yu} and Goh, {Shuang Ru} and Yueming Chen and Yong, {Victor H.K.} and Khan, {Muhammad Imran} and Olawoye, {Olusola O.} and Ashaye, {Adeyinka O.} and Idakwo Ugbede and Adeola Onakoya and Nkiru Kizor-Akaraiwe and Chaiwat Teekhasaenee and Yanin Suwan and Wasu Supakontanasan and Suhanya Okeke and Uche, {Nkechi J.} and Ifeoma Asimadu and Humaira Ayub and Farah Akhtar and Ewa Kosior-Jarecka and Urszula Lukasik and Ignacio Lischinsky and Vania Castro and Grossmann, {Rodolfo Perez} and Megevand, {Gordana Sunaric} and Sylvain Roy and Edward Dervan and Eoin Silke and Aparna Rao and Priti Sahay and Pablo Fornero and Osvaldo Cuello and Delia Sivori and Tamara Zompa and Mills, {Richard A.} and Emmanuelle Souzeau and Paul Mitchell and Wang, {Jie Jin} and Hewitt, {Alex W.} and Michael Coote and Crowston, {Jonathan G.} and Astakhov, {Sergei Y.} and Akopov, {Eugeny L.} and Anton Emelyanov and Vera Vysochinskaya and Gyulli Kazakbaeva and Rinat Fayzrakhmanov and Al-Obeidan, {Saleh A.} and Ohoud Owaidhah and Aljasim, {Leyla Ali} and Balram Chowbay and Foo, {Jia Nee} and Soh, {Raphael Q.} and Sim, {Kar Seng} and Zhicheng Xie and Cheong, {Augustine W.O.} and Mok, {Shi Qi} and Soo, {Hui Meng} and Chen, {Xiao Yin} and Peh, {Su Qin} and Heng, {Khai Koon} and Rahat Husain and Ho, {Su Ling} and Hillmer, {Axel M.} and Cheng, {Ching Yu} and Escudero-Dom{\'i}nguez, {Francisco A.} and Rogelio Gonz{\'a}lez-Sarmiento and Frederico Martinon-Torres and Antonio Salas and Kessara Pathanapitoon and Linda Hansapinyo and Boonsong Wanichwecharugruang and Naris Kitnarong and Anavaj Sakuntabhai and Nguyn, {Hip X.} and Nguyn, {Giang T.T.} and Nguyn, {Tr{\`i}nh V.} and Werner Zenz and Alexander Binder and Klobassa, {Daniela S.} and Hibberd, {Martin L.} and Sonia Davila and Stefan Herms and N{\"o}then, {Markus M.} and Susanne Moebus and Rautenbach, {Robyn M.} and Ari Ziskind and Carmichael, {Trevor R.} and Michele Ramsay and Lydia {\'A}lvarez and Montserrat Garc{\'i}a and H{\'e}ctor Gonz{\'a}lez-Iglesias and Rodr{\'i}guez-Calvo, {Pedro P.} and Cueto, {Luis Fern{\'a}ndez Vega} and {\cC}ilingir Oguz and Nevbahar Tamcelik and Eray Atalay and Bilge Batu and Dilek Aktas and Burcu Kaslm and Wilson, {M. Roy} and Coleman, {Anne L.} and Yutao Liu and Pratap Challa and Leon Herndon and Kuchtey, {Rachel W.} and John Kuchtey and Karen Curtin and Chaya, {Craig J.} and Alan Crandall and Zangwill, {Linda M.} and Wong, {Tien Yin} and Masakazu Nakano and Shigeru Kinoshita and {Den Hollander}, {Anneke I.} and Eija Vesti and Fingert, {John H.} and Lee, {Richard K.} and Sit, {Arthur J.} and Shingleton, {Bradford J.} and Ningli Wang and Daniele Cusi and Raheel Qamar and Peter Kraft and Pericak-Vance, {Margaret A.} and Soumya Raychaudhuri and Steffen Heegaard and Tero Kivel{\"a} and Andr{\'e} Reis and Kruse, {Friedrich E.} and Weinreb, {Robert N.} and Pasquale, {Louis R.} and Haines, {Jonathan L.} and Unnur Thorsteinsdottir and Fridbert Jonasson and Allingham, {R. Rand} and Dan Milea and Robert Ritch and Toshiaki Kubota and Kei Tashiro and Vithana, {Eranga N.} and Shazia Micheal and Fotis Topouzis and Craig, {Jamie E.} and Michael Dubina and Periasamy Sundaresan and Kari Stefansson and Wiggs, {Janey L.} and Francesca Pasutto and Khor, {Chiea Chuen}",
year = "2017",
month = "7",
day = "1",
doi = "10.1038/ng.3875",
language = "English (US)",
volume = "49",
pages = "993--1004",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

AU - Aung, Tin

AU - Ozaki, Mineo

AU - Lee, Mei Chin

AU - Schlötzer-Schrehardt, Ursula

AU - Thorleifsson, Gudmar

AU - Mizoguchi, Takanori

AU - Igo, Robert P.

AU - Haripriya, Aravind

AU - Williams, Susan E.

AU - Astakhov, Yury S.

AU - Orr, Andrew C.

AU - Burdon, Kathryn P.

AU - Nakano, Satoko

AU - Mori, Kazuhiko

AU - Abu-Amero, Khaled

AU - Hauser, Michael

AU - Li, Zheng

AU - Prakadeeswari, Gopalakrishnan

AU - Bailey, Jessica N.Cooke

AU - Cherecheanu, Alina Popa

AU - Kang, Jae H.

AU - Nelson, Sarah

AU - Hayashi, Ken

AU - Manabe, Shin Ichi

AU - Kazama, Shigeyasu

AU - Zarnowski, Tomasz

AU - Inoue, Kenji

AU - Irkec, Murat

AU - Coca-Prados, Miguel

AU - Sugiyama, Kazuhisa

AU - Järvelä, Irma

AU - Schlottmann, Patricio

AU - Lerner, S. Fabian

AU - Lamari, Hasnaa

AU - Nilgün, Yildirim

AU - Bikbov, Mukharram

AU - Park, Ki Ho

AU - Cha, Soon Cheol

AU - Yamashiro, Kenji

AU - Zenteno, Juan C.

AU - Jonas, Jost B.

AU - Kumar, Rajesh S.

AU - Perera, Shamira A.

AU - Chan, Anita S.Y.

AU - Kobakhidze, Nino

AU - George, Ronnie

AU - Vijaya, Lingam

AU - Do, Tan

AU - Edward, Deepak P.

AU - De Juan Marcos, Lourdes

AU - Pakravan, Mohammad

AU - Moghimi, Sasan

AU - Ideta, Ryuichi

AU - Bach-Holm, Daniella

AU - Kappelgaard, Per

AU - Wirostko, Barbara

AU - Thomas, Samuel

AU - Gaston, Daniel

AU - Bedard, Karen

AU - Greer, Wenda L.

AU - Yang, Zhenglin

AU - Chen, Xueyi

AU - Huang, Lulin

AU - Sang, Jinghong

AU - Jia, Hongyan

AU - Jia, Liyun

AU - Qiao, Chunyan

AU - Zhang, Hui

AU - Liu, Xuyang

AU - Zhao, Bowen

AU - Wang, Ya Xing

AU - Xu, Liang

AU - Leruez, Stéphanie

AU - Reynier, Pascal

AU - Chichua, George

AU - Tabagari, Sergo

AU - Uebe, Steffen

AU - Zenkel, Matthias

AU - Berner, Daniel

AU - Mossböck, Georg

AU - Weisschuh, Nicole

AU - Hoja, Ursula

AU - Welge-Luessen, Ulrich Christoph

AU - Mardin, Christian

AU - Founti, Panayiota

AU - Chatzikyriakidou, Anthi

AU - Pappas, Theofanis

AU - Anastasopoulos, Eleftherios

AU - Lambropoulos, Alexandros

AU - Ghosh, Arkasubhra

AU - Shetty, Rohit

AU - Porporato, Natalia

AU - Saravanan, Vijayan

AU - Venkatesh, Rengaraj

AU - Shivkumar, Chandrashekaran

AU - Kalpana, Narendran

AU - Sarangapani, Sripriya

AU - Kanavi, Mozhgan R.

AU - Beni, Afsaneh Naderi

AU - Yazdani, Shahin

AU - Lashay, Alireza

AU - Naderifar, Homa

AU - Khatibi, Nassim

AU - Fea, Antonio

AU - Lavia, Carlo

AU - Dallorto, Laura

AU - Rolle, Teresa

AU - Frezzotti, Paolo

AU - Paoli, Daniela

AU - Salvi, Erika

AU - Manunta, Paolo

AU - Mori, Yosai

AU - Miyata, Kazunori

AU - Higashide, Tomomi

AU - Chihara, Etsuo

AU - Ishiko, Satoshi

AU - Yoshida, Akitoshi

AU - Yanagi, Masahide

AU - Kiuchi, Yoshiaki

AU - Ohashi, Tsutomu

AU - Sakurai, Toshiya

AU - Sugimoto, Takako

AU - Chuman, Hideki

AU - Aihara, Makoto

AU - Inatani, Masaru

AU - Miyake, Masahiro

AU - Gotoh, Norimoto

AU - Matsuda, Fumihiko

AU - Yoshimura, Nagahisa

AU - Ikeda, Yoko

AU - Ueno, Morio

AU - Sotozono, Chie

AU - Jeoung, Jin Wook

AU - Sagong, Min

AU - Park, Kyu Hyung

AU - Ahn, Jeeyun

AU - Cruz-Aguilar, Marisa

AU - Ezzouhairi, Sidi M.

AU - Rafei, Abderrahman

AU - Chong, Yaan Fun

AU - Ng, Xiao Yu

AU - Goh, Shuang Ru

AU - Chen, Yueming

AU - Yong, Victor H.K.

AU - Khan, Muhammad Imran

AU - Olawoye, Olusola O.

AU - Ashaye, Adeyinka O.

AU - Ugbede, Idakwo

AU - Onakoya, Adeola

AU - Kizor-Akaraiwe, Nkiru

AU - Teekhasaenee, Chaiwat

AU - Suwan, Yanin

AU - Supakontanasan, Wasu

AU - Okeke, Suhanya

AU - Uche, Nkechi J.

AU - Asimadu, Ifeoma

AU - Ayub, Humaira

AU - Akhtar, Farah

AU - Kosior-Jarecka, Ewa

AU - Lukasik, Urszula

AU - Lischinsky, Ignacio

AU - Castro, Vania

AU - Grossmann, Rodolfo Perez

AU - Megevand, Gordana Sunaric

AU - Roy, Sylvain

AU - Dervan, Edward

AU - Silke, Eoin

AU - Rao, Aparna

AU - Sahay, Priti

AU - Fornero, Pablo

AU - Cuello, Osvaldo

AU - Sivori, Delia

AU - Zompa, Tamara

AU - Mills, Richard A.

AU - Souzeau, Emmanuelle

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Hewitt, Alex W.

AU - Coote, Michael

AU - Crowston, Jonathan G.

AU - Astakhov, Sergei Y.

AU - Akopov, Eugeny L.

AU - Emelyanov, Anton

AU - Vysochinskaya, Vera

AU - Kazakbaeva, Gyulli

AU - Fayzrakhmanov, Rinat

AU - Al-Obeidan, Saleh A.

AU - Owaidhah, Ohoud

AU - Aljasim, Leyla Ali

AU - Chowbay, Balram

AU - Foo, Jia Nee

AU - Soh, Raphael Q.

AU - Sim, Kar Seng

AU - Xie, Zhicheng

AU - Cheong, Augustine W.O.

AU - Mok, Shi Qi

AU - Soo, Hui Meng

AU - Chen, Xiao Yin

AU - Peh, Su Qin

AU - Heng, Khai Koon

AU - Husain, Rahat

AU - Ho, Su Ling

AU - Hillmer, Axel M.

AU - Cheng, Ching Yu

AU - Escudero-Domínguez, Francisco A.

AU - González-Sarmiento, Rogelio

AU - Martinon-Torres, Frederico

AU - Salas, Antonio

AU - Pathanapitoon, Kessara

AU - Hansapinyo, Linda

AU - Wanichwecharugruang, Boonsong

AU - Kitnarong, Naris

AU - Sakuntabhai, Anavaj

AU - Nguyn, Hip X.

AU - Nguyn, Giang T.T.

AU - Nguyn, Trình V.

AU - Zenz, Werner

AU - Binder, Alexander

AU - Klobassa, Daniela S.

AU - Hibberd, Martin L.

AU - Davila, Sonia

AU - Herms, Stefan

AU - Nöthen, Markus M.

AU - Moebus, Susanne

AU - Rautenbach, Robyn M.

AU - Ziskind, Ari

AU - Carmichael, Trevor R.

AU - Ramsay, Michele

AU - Álvarez, Lydia

AU - García, Montserrat

AU - González-Iglesias, Héctor

AU - Rodríguez-Calvo, Pedro P.

AU - Cueto, Luis Fernández Vega

AU - Oguz, Çilingir

AU - Tamcelik, Nevbahar

AU - Atalay, Eray

AU - Batu, Bilge

AU - Aktas, Dilek

AU - Kaslm, Burcu

AU - Wilson, M. Roy

AU - Coleman, Anne L.

AU - Liu, Yutao

AU - Challa, Pratap

AU - Herndon, Leon

AU - Kuchtey, Rachel W.

AU - Kuchtey, John

AU - Curtin, Karen

AU - Chaya, Craig J.

AU - Crandall, Alan

AU - Zangwill, Linda M.

AU - Wong, Tien Yin

AU - Nakano, Masakazu

AU - Kinoshita, Shigeru

AU - Den Hollander, Anneke I.

AU - Vesti, Eija

AU - Fingert, John H.

AU - Lee, Richard K.

AU - Sit, Arthur J.

AU - Shingleton, Bradford J.

AU - Wang, Ningli

AU - Cusi, Daniele

AU - Qamar, Raheel

AU - Kraft, Peter

AU - Pericak-Vance, Margaret A.

AU - Raychaudhuri, Soumya

AU - Heegaard, Steffen

AU - Kivelä, Tero

AU - Reis, André

AU - Kruse, Friedrich E.

AU - Weinreb, Robert N.

AU - Pasquale, Louis R.

AU - Haines, Jonathan L.

AU - Thorsteinsdottir, Unnur

AU - Jonasson, Fridbert

AU - Allingham, R. Rand

AU - Milea, Dan

AU - Ritch, Robert

AU - Kubota, Toshiaki

AU - Tashiro, Kei

AU - Vithana, Eranga N.

AU - Micheal, Shazia

AU - Topouzis, Fotis

AU - Craig, Jamie E.

AU - Dubina, Michael

AU - Sundaresan, Periasamy

AU - Stefansson, Kari

AU - Wiggs, Janey L.

AU - Pasutto, Francesca

AU - Khor, Chiea Chuen

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.3875

DO - 10.1038/ng.3875

M3 - Article

VL - 49

SP - 993

EP - 1004

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -