Letter | Published:

Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma

Nature Genetics volume 48, pages 556562 (2016) | Download Citation

Abstract

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10−15), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10−16), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10−14), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10−11), and DPM2FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10−12). We also confirmed significant association at three previously described loci (P < 5 × 10−8 for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1ST18)1, providing new insights into the biology of PACG.

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Acknowledgements

This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Translational and Clinical Research (TCR) Flagship Programme Grant Stratified Medicine for Primary Angle Closure Glaucoma (NMRC/TCR/008-SERI/2013) and the Singapore Translational Research (STaR) Investigator Award Singapore Angle Closure Glaucoma Program Characterization, Prevention, and Management (NMRC/STAR/0023/2014), as well as the Biomedical Research Council, Agency for Science, Technology and Research (A-STAR), Singapore. A.T.L.-S. gratefully acknowledges support from grants RUI 1001/PPSP/812101 and RUI 1001/PPSP/812152 from the Universiti Sains Malaysia. H.J., C.Q., and N. Wang acknowledge support from the Program of Beijing Scholars (2013), Leading Talents–High-Level Talents of the Health System of Beijing (2009-1-05), and the National Major Scientific and Technological Special Project for 'Significant New Drugs Development' (2011ZX09302-007-05), as well as Project of the National Natural Science Foundation of China (81570837) grants.

Author information

Author notes

    • Chiea Chuen Khor
    • , Tan Do
    • , Hongyan Jia
    • , Masakazu Nakano
    • , Ronnie George
    • , Khaled Abu-Amero
    • , Roopam Duvesh
    •  & Li Jia Chen

    These authors contributed equally to this work.

    • Nhu Hon Do
    • , Periasamy Sundaresan
    • , Clement C Tham
    • , Paul J Foster
    • , Lingam Vijaya
    • , Kei Tashiro
    • , Eranga N Vithana
    • , Ningli Wang
    •  & Tin Aung

    These authors jointly directed this work.

Affiliations

  1. Genome Institute of Singapore, A-STAR, Singapore.

    • Chiea Chuen Khor
    • , Zheng Li
    • , Zhicheng Xie
    • , Xiao Yin Chen
    • , Jia Nee Foo
    • , Kar Seng Sim
    • , Martin L Hibberd
    • , Eileen Png
    •  & Yik Y Teo
  2. Singapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke–National University of Singapore, Singapore.

    • Chiea Chuen Khor
    • , Monisha E Nongpiur
    • , Shamira A Perera
    • , Mei-Chin Lee
    • , Anita S Chan
    • , Rahat Husain
    • , Aliza Jap
    • , Mani Baskaran
    • , David Goh
    • , Daniel H Su
    • , Tina T Wong
    • , Desmond T Quek
    • , Victor H Yong
    • , Xiao-Yu Ng
    • , Shuang Ru Goh
    • , Yaan Fun Chong
    • , R Rand Allingham
    • , Michael A Hauser
    • , Ching-Lin Ho
    • , Donald T Tan
    • , Seang Mei Saw
    • , Ching-Yu Cheng
    • , Tien Y Wong
    • , Lingam Vijaya
    • , Eranga N Vithana
    •  & Tin Aung
  3. Department of Biochemistry, National University of Singapore, Singapore.

    • Chiea Chuen Khor
  4. Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.

    • Tan Do
    • , Thi Lam Huong Dao
    • , Thi Thuy Giang Nguyen
    • , Tien Dat Tran
    •  & Nhu Hon Do
  5. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China.

    • Hongyan Jia
    • , Chunyan Qiao
    • , Huaizhou Wang
    •  & Ningli Wang
  6. Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.

    • Masakazu Nakano
    •  & Kei Tashiro
  7. Jadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Sankara Nethralaya, Chennai, India.

    • Ronnie George
    • , Balekudaru Shantha
    •  & Lingam Vijaya
  8. Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

    • Khaled Abu-Amero
    •  & Saleh Al-Obeidan
  9. Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA.

    • Khaled Abu-Amero
  10. Department of Genetics, Aravind Medical Research Foundation, Madurai, India.

    • Roopam Duvesh
    • , Saravanan Vijayan
    •  & Periasamy Sundaresan
  11. Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.

    • Li Jia Chen
    • , Pancy O S Tam
    • , Chi Pui Pang
    •  & Clement C Tham
  12. Department of Ophthalmology, Tan Tock Seng Hospital, NHG Eye Institute, Singapore.

    • Hon-Tym Wong
    • , Vernon K Yong
    • , Leonard W Yip
    • , Boon-Ang Lim
    • , Jeanne Ogle
    •  & Owen Hee
  13. Department of Ophthalmology, University of the Ryukyus, Okinawa, Nishihara, Japan.

    • Hiroshi Sakai
    •  & Michiko Yonahara
  14. Center of Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil.

    • Mônica Barbosa de Melo
    •  & Bruno B de Souza
  15. Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia and Hospital Universiti Sains Malaysia, Kelantan, Malaysia.

    • Yaakub Azhany
    •  & Ahmad Tajudin Liza-Sharmini
  16. Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

    • Yoko Ikeda
    • , Morio Ueno
    • , Kazuhiko Mori
    •  & Shigeru Kinoshita
  17. Instituto de Glaucoma y Catarata, Lima, Peru.

    • Rodolfo A Perez-Grossmann
  18. Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.

    • Tomasz Zarnowski
    • , Ewa Kosior-Jarecka
    •  & Urszula Lukasik
  19. NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK.

    • Alexander C Day
    • , Yuzhen Jiang
    • , Naushin Waseem
    • , Sancy Low
    •  & Paul J Foster
  20. Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK.

    • Alexander C Day
    • , Yuzhen Jiang
    • , Sancy Low
    •  & Paul J Foster
  21. Division of Genetics, UCL Institute of Ophthalmology, London, UK.

    • Alexander C Day
    • , Yuzhen Jiang
    • , Naushin Waseem
    • , Sancy Low
    • , Shomi S Bhattacharya
    •  & Paul J Foster
  22. Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht Karls University Heidelberg, Heidelberg, Germany.

    • Jost B Jonas
  23. Ho Chi Minh City Eye Hospital, Ho Chi Minh City, Vietnam.

    • Tuan Anh Tran
    • , Tuyet Bach Trinh
    • , Huan Nguyen Pham
    •  & Huong T T Bui
  24. Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.

    • Humaira Ayub
    •  & Raheel Qamar
  25. Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan.

    • Farah Akhtar
  26. Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands.

    • Shazia Micheal
    •  & Anneke I den Hollander
  27. Department of Ophthalmology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • Paul T K Chew
    • , Chelvin C Sng
    • , Maria C Aquino
    • , Seng-Chee Loon
    • , Ching-Yu Cheng
    •  & Tin Aung
  28. King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

    • Leyla A Aljasim
    • , Sami Al-Shahwan
    • , E Randy Craven
    •  & Deepak P Edward
  29. All India Institute of Medical Sciences, New Delhi, India.

    • Tanuj Dada
    • , Rrima Dada
    • , Kuldeep Mohanty
    • , Muneeb A Faiq
    •  & Ramanjit Sihota
  30. Department of Glaucoma, Da Nang Eye Hospital, Da Nang City, Vietnam.

    • Tam Thi Luu
    •  & Vi Huyen Doan
  31. Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.

    • Mona S Awadalla
    • , Kathryn P Burdon
    •  & Jamie E Craig
  32. Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

    • Naris Kitnarong
  33. Glaucoma Services, Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand.

    • Boonsong Wanichwecharungruang
  34. College of Medicine, Rangsit University, Bangkok, Thailand.

    • Boonsong Wanichwecharungruang
  35. Mandalay Eye Department, Mandalay Eye ENT Hospital, University of Medicine Mandalay, Mandalay, Myanmar.

    • Yee Yee Aung
    •  & Saw Htoo Set
  36. Department of Ophthalmology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.

    • Jelinar Mohamed-Noor
    • , Eng Hui Gan
    •  & Thayanithi Sandragasu
  37. Vision Research Foundation, Sankara Nethralaya, Chennai, India.

    • Sripriya Sarangapani
    •  & Nagaswamy Soumittra
  38. Division of Ophthalmology, Changi General Hospital, Singapore.

    • Rahat Husain
    •  & Aliza Jap
  39. Department of Ophthalmology, Thammasat University Faculty of Medicine, Rangsit, Thailand.

    • Manchima Makornwattana
    • , Anuwat Prutthipongsit
    • , Thipnapa Patthanathamrongkasem
    •  & Nuttamon Srisamran
  40. Eye Department, Viet Tiep General Hospital, Hai Phong, Vietnam.

    • Thanh Thu Nguyen
    •  & Tung S Hoan
  41. Asian Eye Institute, Manila, Philippines.

    • Edgar U Leuenberger
    • , Mary Ann T Catacutan
    • , Irene R Felarca
    • , Chona S Liao
    •  & Jovell Ian M Peregrino
  42. Division of Ophthalmology, University of the East, Manila, Philippines.

    • Edgar U Leuenberger
  43. Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.

    • Ki-Ho Park
    •  & Jin Wook Jeoung
  44. Glaucoma Service Jakarta Eye Center, Jakarta, Indonesia.

    • Widya Artini Wiyogo
    • , Emma Rusmayani
    • , Vira Wardhana Istiantoro
    •  & Zeiras Eka Djamal
  45. Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.

    • Widya Artini Wiyogo
  46. Narayana Nethralaya Eye Hospital, Bangalore, India.

    • Rajesh S Kumar
    • , Rohit Shetty
    •  & Arkasubhra Ghosh
  47. Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA.

    • Celso Tello
    •  & Robert Ritch
  48. Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan.

    • Yasuo Kurimoto
    •  & Masako Kuroda
  49. Nepal Glaucoma Eye Clinic, Tilganga Institute of Ophthalmology, Kathmandu, Nepal.

    • Suman S Thapa
  50. Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

    • Kessara Pathanapitoon
  51. Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.

    • John F Salmon
    •  & Christine A Kiire
  52. Department of Ophthalmology, Konyang University, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Seoul, Republic of Korea.

    • Yong Ho Sohn
    •  & Young Hoon Hwang
  53. Dipartimento di Scienze Chirurgiche, Università di Torino, Turin, Italy.

    • Antonio Fea
    • , Giulia Consolandi
    • , Giulia Pignata
    • , Carlo Lavia
    •  & Laura Dallorto
  54. Ozaki Eye Hospital, Hyuga, Japan.

    • Mineo Ozaki
  55. Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

    • Mineo Ozaki
  56. Department of Ophthalmology, University of Hong Kong, Hong Kong, China.

    • Jimmy S M Lai
    • , Bonnie N K Choy
    •  & Jennifer W H Shum
  57. Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

    • Visanee Tantisevi
    • , Prin Rojanapongpun
    •  & Anita Manassakorn
  58. Department of Ophthalmology, No. 1 Defence Services General Hospital, Yangon, Myanmar.

    • Chaw Chaw Khaing
    •  & Nay Lin Oo
  59. Mizoguchi Eye Hospital, Sasebo, Japan.

    • Takanori Mizoguchi
  60. Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan.

    • Satoko Nakano
    •  & Toshiaki Kubota
  61. Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.

    • Chan-Yun Kim
    •  & Hyoung Won Bae
  62. Shijiazhuang First Eye Hospital, Shijiazhuang, China.

    • Guangxian Tang
  63. Handan Eye Hospital, Handan, China.

    • Sujie Fan
  64. Eye Institute and Affiliated Xiamen Eye Center, Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.

    • Renyi Wu
  65. Anyang Eye Hospital, Anyang, China.

    • Hailin Meng
  66. Department of Ophthalmology, Pasig City General Hospital, Pasig City, Philippines.

    • Jose Maria Martinez
  67. University of Malaya, Eye Research Centre, Kuala Lumpur, Malaysia.

    • Norlina Ramli
    •  & Mimiwati Zahari
  68. Department of Ophthalmology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

    • Norlina Ramli
    •  & Mimiwati Zahari
  69. Myanmar Eye Centre, Pun Hlaing Silom Hospital, Yangon, Myanmar.

    • Yin Mon Aung
    • , Khin Thida Oo
    • , Aye Thi Han
    •  & Su Nyunt Zaw
  70. Myanmar Eye Centre, Shwe La Min Hospital, Yangon, Myanmar.

    • Yin Mon Aung
    • , Khin Thida Oo
    • , Aye Thi Han
    •  & Su Nyunt Zaw
  71. Department of Ophthalmology/Glaucoma Section, Asian Hospital and Medical Center, Muntinlupa City, Philippines.

    • Rigo Daniel Reyes
    •  & Raquel Quino
  72. Binan Doctors Eye Center, Binan Doctors Hospital, Laguna, Philippines.

    • Rigo Daniel Reyes
  73. Department of Ophthalmology, University Hospital Nottingham, University of Nottingham, Nottingham, UK.

    • Stephen A Vernon
    •  & Richard Stead
  74. BMI Park Hospital Nottingham, Nottingham, UK.

    • Stephen A Vernon
  75. International Specialist Eye Centre, Kuala Lumpur, Malaysia.

    • Seng Kheong Fang
  76. Glaucoma Clinic, Aravind Eye Hospital, Pondicherry, India.

    • Rengaraj Venkatesh
    •  & Srinivasan Kavitha
  77. Glaucoma Clinic, Aravind Eye Hospital, Madurai, India.

    • Subbiah R Krishnadas
    • , Vital P Costa
    •  & Ricardo Y Abe
  78. Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.

    • José P C de Vasconcellos
    •  & Jamil Miguel Neto
  79. Instituto de Ciencias Médicas, Lima, Peru.

    • Guillermo Barreto Fong
  80. Hospital Nacional Arzobispo Loayza, Lima, Peru.

    • Vania Castro Tamanaja
  81. Centro de Genética y Biología Molecular, Universidad de San Martín de Porres, Lima, Peru.

    • Ricardo Fujita
    •  & Maria L Guevara-Fujita
  82. Wilmer Eye Institute, Johns Hopkins Hospital School of Medicine, Baltimore, Maryland, USA.

    • E Randy Craven
    •  & Deepak P Edward
  83. Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.

    • Muhammad Imran Khan
    •  & Anneke I den Hollander
  84. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

    • Alex W Hewitt
    •  & Kathryn P Burdon
  85. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.

    • Alex W Hewitt
  86. Department of Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

    • Lerprat Mangkornkanokpong
    • , Sunee Chansangpetch
    •  & Wing Lau Ho
  87. Department of Ophthalmology, Queen Mary Hospital, Hong Kong, China.

    • Jonathan C H Chan
  88. Department of Ophthalmology, North Okkalarpa General Hospital, Yangon, Myanmar.

    • Hlaing May Than
  89. Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.

    • Mark Seielstad
  90. Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

    • Sarah J Dunstan
  91. Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.

    • Sarah J Dunstan
  92. Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.

    • Nguyen Van Vinh Chau
  93. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

    • Jinxin Bei
    •  & Yi Xin Zeng
  94. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.

    • Jinxin Bei
    •  & Yi Xin Zeng
  95. Peking Union Medical College, Beijing, China.

    • Yi Xin Zeng
  96. Oxford University Clinical Research Unit–Nepal, Patan Academy of Health Sciences, Patan Hospital, Patan, Nepal.

    • Abhilasha Karkey
    •  & Buddha Basnyat
  97. Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

    • Francesca Pasutto
  98. Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy.

    • Daniela Paoli
  99. Department of Surgery, Section of Ophthalmology, University of Siena, Siena, Italy.

    • Paolo Frezzotti
  100. Centre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.

    • Jie Jin Wang
    •  & Paul Mitchell
  101. Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

    • John H Fingert
  102. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA.

    • John H Fingert
  103. Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA.

    • R Rand Allingham
    •  & Michael A Hauser
  104. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

    • Michael A Hauser
  105. Division of Medical Oncology, National Cancer Centre, Singapore.

    • Soon Thye Lim
  106. Department of Economics, National University of Singapore, Singapore.

    • Soo Hong Chew
  107. Department of Psychology, National University of Singapore, Singapore.

    • Richard P Ebstein
  108. Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Department of Genomes and Genetics, Paris, France.

    • Anavaj Sakuntabhai
  109. Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Paris, France.

    • Anavaj Sakuntabhai
  110. Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea.

    • Kyu Hyung Park
  111. Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.

    • Jeeyun Ahn
  112. Department of Medical Microbiology and Virology, University Medical Center Utrecht, Utrecht, the Netherlands.

    • Greet Boland
    •  & Harm Snippe
  113. GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India.

    • Arkasubhra Ghosh
  114. Department of Biochemistry, Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan.

    • Raheel Qamar
  115. Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

    • Ya-Xing Wang
    • , Yik Y Teo
    • , Liang Xu
    •  & Ningli Wang
  116. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Yik Y Teo
    • , E-Shyong Tai
    •  & Seang Mei Saw
  117. Life Sciences Institute, National University of Singapore, Singapore.

    • Yik Y Teo
  118. National University of Singapore Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.

    • Yik Y Teo
  119. Department of Statistics and Applied Probability, National University of Singapore, Singapore.

    • Yik Y Teo
  120. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • E-Shyong Tai
  121. Department of Glaucoma, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico.

    • Curt Hartleben-Matkin
  122. Department of Genetics, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico.

    • David Lozano-Giral
    •  & Juan C Zenteno
  123. Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.

    • Juan C Zenteno

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Contributions

T.A. and C.C. Khor conceived the project. T. Do., H.J., M.N., R.G., K.A.-A., R. Duvesh., L.J.C., Z.L., M.E.N., S.A.P., C.Q., H.-T.W., H. Sakai., M.B.d.M., Y.A., T.L.H.D., Y.I., R.A.P.-G., T.Z., A.C.D., J.B.J., P.O.S.T., T.A.T., H.A., F.A., S.M., P.T.K.C., L.A.A., T. Dada., T.T.L., M.S.A., N.K., B.W., Y.Y.A., J.M.-N., S.V., S.S., R.H., A.J., M.B., D.G., D.H.S., H.W., V.K.Y., L.W.Y., T.B.T., M.M., T.T.N., E.U.L., K.-H.P., W.A.W., R.S.K., C.T., Y.K., S.S.T., K.P., J.F.S., Y.H.S., A.F., M.O., J.S.M.L., V.T., C.C. Khaing., T.M., S.N., C.-Y.K., G.T., S.F., R.W., H.M., T.T.G.N., T.D.T., M.U., J.M.M., N.R., Y.M.A., R.D.R., S.A.V., S.K.F., Z.X., X.Y.C., J.N.F., K.S.S., T.T.W., D.T.Q., R.V., S. Kavitha., S.R.K., N. Soumittra., B.S., B.-A.L., J.O., J.P.C.d.V., V.P.C., R.Y.A., B.B.d.S., C.C.S., M.C.A., E.K.-J., G.B.F., V.C.T., R.F., Y.J., N. Waseem., S.L., H.N.P., S.A.-S., E.R.C., M.I.K., R. Dada., K. Mohanty., M.A.F., A.W.H., K.P.B., E.H.G., A.P., T.P., M.A.T.C., I.R.F., C.S.L., E.R., V.W.I., G.C., G.P., C.L., P.R., L.M., S.C., J.C.H.C., B.N.K.C., J.W.H.S., H.M.T., K.T.O., A.T.H., V.H.Y., X.-Y.N., F.P., D.P., P.F., J.J.W., P.M., J.H.F., R.R.A., M.A.H., R. Stead., R. Quino., S.N.Z., U.L., R. Shetty., M.Z., H.W.B., N.L.O., T.K., A.M., W.L.H., L.D., Y.H.H., C.A.K., M.K., Z.E.D., J.I.M.P., A.G., J.W.J., T.S.H., N. Srisamran, T.S., S.H.S., V.H.D., S.S.B., C.-L.H., D.T.T., R. Sihota., S.-C.L., K. Mori., S. Kinoshita., A.I.d.H., R. Qamar., Y.-X.W., Y.Y.T., E.-S.T., C.H.-M., D.L.-G., S.M.S., C.-Y.C., J.C.Z., C.P.P., H.T.T.B., O.H., J.E.C., D.P.E., M.Y., J.M.N., M.L.G.-F., L.X., R.R., A.T.L.-S., T.Y.W., S.A.-O., N.H.D., P.S., C.C.T., P.J.F., L.V., K.T., E.N.V., and N. Wang were responsible for sample collection, data analysis, and sample administration. M.L.H., M.S., E.P., S.J.D., N.V.V.C., J.B., Y.X.Z., A.K., S.T.L., S.H.C., R.P.E., A.S., K.H.P., J.A., G.B., H. Snippe., and B.B. contributed control data sets with genome-wide genotyping data. M.-C.L., A.S.C., S.R.G., Y.F.C., and E.N.V. were responsible for molecular biology work and pathological tissue staining and interpretation. The manuscript was written by C.C. Khor, with approval from all authors. All authors read and approved the final version of the manuscript for publication. T.A. was responsible for obtaining financial support for the study.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Chiea Chuen Khor or Ningli Wang or Tin Aung.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–12, Supplementary Note and Supplementary Tables 1–8, 10 and 11.

Excel files

  1. 1.

    Supplementary Table 9

    Variants located within predicted regulatory regions and in LD (r2 >0.8) with the top SNPs in the five newly identified loci.

Text files

  1. 1.

    Supplementary Data Set

    Summary association statistics of the PACG GWAS SNPs with direct microarray genotyping together with imputation fine-mapping of the genome-wide significant loci.

About this article

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DOI

https://doi.org/10.1038/ng.3540

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