Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Henriët Springelkamp, René Höhn, Aniket Mishra, Pirro G Hysi, Chiea-Chuen Khor, Stephanie J Loomis, Jessica N Cooke Bailey, Jane Gibson, Gudmar Thorleifsson, Sarah F Janssen, Xiaoyan Luo, Wishal D Ramdas, Eranga Vithana, Monisha E Nongpiur, Grant W Montgomery, Liang Xu, Jenny E Mountain, Puya Gharahkhani, Yi Lu, Najaf AminLennart C Karssen, Kar-Seng Sim, Elisabeth M van Leeuwen, Adriana I Iglesias, Virginie J M Verhoeven, Michael A Hauser, Seng-Chee Loon, Dominiek D G Despriet, Abhishek Nag, Cristina Venturini, Paul G Sanfilippo, Arne Schillert, Jae H Kang, John Landers, Fridbert Jonasson, Angela J Cree, Leonieke M E van Koolwijk, Fernando Rivadeneira, Emmanuelle Souzeau, Vesteinn Jonsson, Geeta Menon, , Robert N Weinreb, Paulus T V M de Jong, Ben A Oostra, André G Uitterlinden, Albert Hofman, Sarah Ennis, Unnur Thorsteinsdottir, Kathryn P Burdon, Hans G Lemij

Research output: Contribution to journalReview articlepeer-review


Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Original languageEnglish
Pages (from-to)4883
JournalNature Communications
Publication statusPublished - 22 Sept 2014


  • Asian Continental Ancestry Group/genetics
  • Case-Control Studies
  • European Continental Ancestry Group/genetics
  • Gene Expression Profiling
  • Gene Frequency
  • Genome-Wide Association Study
  • Genotype
  • Glaucoma/ethnology
  • Humans
  • Optic Disk/pathology
  • Optic Nerve/pathology
  • Phenotype
  • Polymorphism, Single Nucleotide


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