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

Springelkamp H1, Höhn R2, Mishra A3, Hysi PG4, Khor CC5, Loomis SJ6, Bailey JN7, Gibson J8, Thorleifsson G9, Janssen SF10, Luo X11, Ramdas WD12,Vithana E13, Nongpiur ME14, Montgomery GW15, Xu L16, Mountain JE17, Gharahkhani P3, Lu Y3, Amin N18, Karssen LC18, Sim KS19, van Leeuwen EM18,Iglesias AI18, Verhoeven VJ1, Hauser MA20, Loon SC21, Despriet DD12, Nag A4, Venturini C22, Sanfilippo PG23, Schillert A24, Kang JH25, Landers J26,Jonasson F27, Cree AJ28, van Koolwijk LM18, Rivadeneira F29, Souzeau E26, Jonsson V30, Menon G31; Blue Mountains Eye Study—GWAS group, Weinreb RN32, de Jong PT33, Oostra BA34, Uitterlinden AG29, Hofman A35, Ennis S36, Thorsteinsdottir U37, Burdon KP26; NEIGHBORHOOD Consortium; Wellcome Trust Case Control Consortium 2 (WTCCC2), Spector TD4, Mirshahi A2, Saw SM38, Vingerling JR1, Teo YY39, Haines JL7, Wolfs RC12, Lemij HG40, Tai ES41,Jansonius NM42, Jonas JB43, Cheng CY13, Aung T14, Viswanathan AC44, Klaver CC1, Craig JE26, Macgregor S3, Mackey DA45, Lotery AJ28, Stefansson K37,Bergen AA46, Young TL11, Wiggs JL6, Pfeiffer N2, Wong TY13, Pasquale LR47, Hewitt AW23, van Duijn CM18, Hammond CJ4.

Abstract

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.