Article open access publication

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

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 47, 4, 2015

DOI:10.1038/ng.3226, Dimensions: pub.1026616396, PMC: PMC4605818, PMID: 25706626,

Authors

Aung, Tin * (1) (2) (3) (4) (5)
Ozaki, Mineo (6) (7)
Li, Zheng (4)
Chan, Anita S Y (2) (3)
Burdon, Kathryn P (14) (15)
Jia, Liyun (24)
Huang, Lulin (28) (29) (30)
Miyata, Kazunori (35) (36)
Leo, Paul (46)
Wong, Tien Yin (2) (3) (5)
Liu, Yutao (48) (49)
Hewitt, Alex W (15) (52)
Chen, Xueyi (55) (56)
Cheng, Ching Yu (2) (5)
Husain, Rahat (2) (3)
Herms, Stefan (59) (60) (61)
Teo, Yik Ying (5) (9)
Heegaard, Steffen (73) (74)
Xu, Liang (24)
Schwab, Matthias (63) (79) (80)
Yang, Zheng-Lin (28) (29) (30)
Edward, Deepak P (23) (84)
Pasquale, Louis R (70) (71)
Dubina, Michael (16) (66)
Khor, Chiea Chuen * (2) (4) (5)

* Corresponding author

Affiliations

Organisations

  1. (1) Duke University–National University of Singapore Graduate Medical School, Singapore
  2. (2) Singapore Eye Research Institute, grid.272555.2
  3. (3) Singapore National Eye Center, grid.419272.b
  4. (4) Genome Institute of Singapore, grid.418377.e
  5. (5) National University of Singapore, grid.4280.e
  6. (6) Ozaki Eye Hospital, Hyuga, Japan
  7. (7) Hayashi Eye Hospital, grid.413786.f
  8. (8) Mizoguchi Eye Hospital, Sasebo, Japan
  9. (9) Duke University, grid.26009.3d
  10. (10) Aravind Eye Hospital, grid.413854.f
  11. (11) Oita University, grid.412334.3
  12. (12) Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen-Nürnberg, Germany
  13. (13) Jackson Laboratory, grid.249880.f
  14. (14) Flinders University, grid.1014.4
  15. (15) University of Tasmania, grid.1009.8
  16. (16) First Pavlov State Medical University of St. Peterburg, grid.412460.5
  17. (17) Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA
  18. (18) King Saud University, grid.56302.32
  19. (19) National Autonomous University of Mexico, grid.9486.3
  20. (20) Eskişehir Osmangazi University, grid.164274.2
  21. (21) Medical University of Lublin, grid.411484.c
  22. (22) Shahid Beheshti University of Medical Sciences, grid.411600.2
  23. (23) King Khaled Eye Specialist Hospital, grid.415329.8
  24. (24) Capital Medical University, grid.24696.3f
  25. (25) University of the Witwatersrand, grid.11951.3d
  26. (26) Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy
  27. (27) Organización Médica de Investigación, Buenos Aires, Argentina
  28. (28) Chinese Academy of Sciences, grid.9227.e
  29. (29) Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, grid.410646.1
  30. (30) University of Electronic Science and Technology of China, grid.54549.39
  31. (31) Kyoto Prefectural University of Medicine, grid.272458.e
  32. (32) Glaucoma Services, Narayana Nethralaya Eye Hospital, Bangalore, India
  33. (33) Shinjo Eye Clinic, Miyazaki, Japan
  34. (34) Ideta Eye Hospital, grid.414536.1
  35. (35) Miyata Eye Hospital, grid.415995.5
  36. (36) University of Miyazaki, grid.410849.0
  37. (37) Kanazawa University, grid.9707.9
  38. (38) Sensho-kai Eye Institute, Kyoto, Japan
  39. (39) Inouye Eye Hospital, grid.414626.3
  40. (40) Asahikawa Medical University, grid.252427.4
  41. (41) Hiroshima University, grid.257022.0
  42. (42) Yotsuya Shirato Eye Clinic, Tokyo, Japan
  43. (43) Ohashi Eye Center, Sapporo, Japan
  44. (44) Tane Memorial Eye Hospital, Osaka, Japan
  45. (45) Kyoto University, grid.258799.8
  46. (46) University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  47. (47) Dalhousie University, grid.55602.34
  48. (48) Augusta University, grid.410427.4
  49. (49) Duke Medical Center, grid.414179.e
  50. (50) Stellenbosch University, grid.11956.3a
  51. (51) Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia
  52. (52) University of Melbourne, grid.1008.9
  53. (53) University of Sydney, grid.1013.3
  54. (54) XinHua Hospital, grid.412987.1
  55. (55) First Affiliated Hospital of Xinjiang Medical University, grid.412631.3
  56. (56) Mount Sinai Hospital, grid.416167.3
  57. (57) Tan Tock Seng Hospital, grid.240988.f
  58. (58) University of Erlangen-Nuremberg, grid.5330.5
  59. (59) University Hospital of Basel, grid.410567.1
  60. (60) University of Basel, grid.6612.3
  61. (61) University of Bonn, grid.10388.32
  62. (62) Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
  63. (63) Universitätsklinikum Tübingen, grid.411544.1
  64. (64) Genes, Repair and Regeneration in Ophthalmic Workstation Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
  65. (65) Centro Oftalmológico Lischinsky, Tucumán, Argentina
  66. (66) Saint Petersburg Academic University, grid.35135.31
  67. (67) Aristotle University of Thessaloniki, grid.4793.9
  68. (68) University of California, Los Angeles, grid.19006.3e
  69. (69) Wayne State University, grid.254444.7
  70. (70) Harvard University, grid.38142.3c
  71. (71) Brigham and Women's Hospital, grid.62560.37
  72. (72) Department of Ophthalmology, Military Hospital Begin, Paris, France
  73. (73) Rigshospitalet, grid.475435.4, Capital Region
  74. (74) University of Copenhagen, grid.5254.6, KU
  75. (75) University of Iowa, grid.214572.7
  76. (76) Heidelberg University, grid.7700.0
  77. (77) New York University, grid.137628.9
  78. (78) National Cancer Centre Singapore, grid.410724.4
  79. (79) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
  80. (80) German Cancer Research Center, grid.7497.d
  81. (81) Fundación para el Estudio del Glaucoma, Buenos Aires, Argentina
  82. (82) University of Siena, grid.9024.f
  83. (83) University of Fukui, grid.163577.1
  84. (84) Johns Hopkins University, grid.21107.35

Description

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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University of Copenhagen

Danish Open Access Indicator

2015: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2015: Level 2

Research area: Medicine

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Times Cited: 57

Field Citation Ratio (FCR): 7.68

Relative Citation ratio (RCR): 2.87

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Green, Accepted