Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process
Springelkamp H., Höhn R., Mishra A., Hysi PG., Khor C-C., Loomis SJ., Bailey JNC., Gibson J., Thorleifsson G., Janssen SF., Luo X., Ramdas WD., Vithana E., Nongpiur ME., Montgomery GW., Xu L., Mountain JE., Gharahkhani P., Lu Y., Amin N., Karssen LC., Sim K-S., van Leeuwen EM., Iglesias AI., Verhoeven VJM., Hauser MA., Loon S-C., Despriet DDG., Nag A., Venturini C., Sanfilippo PG., Schillert A., Kang JH., Landers J., Jonasson F., Cree AJ., van Koolwijk LME., Rivadeneira F., Souzeau E., Jonsson V., Menon G., Mitchell P., Wang JJ., Rochtchina E., Attia J., Scott R., Holliday EG., Wong T-Y., Baird PN., Xie J., Inouye M., Viswanathan A., Sim X., Weinreb RN., de Jong PTVM., Oostra BA., Uitterlinden AG., Hofman A., Ennis S., Thorsteinsdottir U., Burdon KP., Allingham RR., Brilliant MH., Budenz DL., Cooke Bailey JN., Christen WG., Fingert J., Friedman DS., Gaasterland D., Gaasterland T., Haines JL., Hauser MA., Kang JH., Kraft P., Lee RK., Lichter PR., Liu Y., Loomis SJ., Moroi SE., Pasquale LR., Pericak-Vance MA., Realini A., Richards JE., Schuman JS., Scott WK., Singh K., Sit AJ., Vollrath D., Weinreb RN., Wiggs JL., Wollstein G., Zack DJ., Zhang K., Donnelly P., Barroso I., Blackwell JM., Bramon E., Brown MA., Casas JP., Corvin A., Deloukas P., Duncanson A., Jankowski J., Markus HS., Mathew CG., Palmer CNA., Plomin R., Rautanen A., Sawcer SJ., Trembath RC., Viswanathan AC., Wood NW., Spencer CCA., Band G., Bellenguez C., Freeman C., Hellenthal G., Giannoulatou E., Pirinen M., Pearson R., Strange A., Su Z., Vukcevic D., Donnelly P., Langford C., Hunt SE., Edkins S., Gwilliam R., Blackburn H., Bumpstead SJ., Dronov S., Gillman M., Gray E., Hammond N., Jayakumar A., McCann OT., Liddle J., Potter SC., Ravindrarajah R., Ricketts M., Waller M., Weston P., Widaa S., Whittaker P., Barroso I., Deloukas P., Mathew CG., Blackwell JM., Brown MA., Corvin A., Spencer CCA., Spector TD., Mirshahi A., Saw S-M., Vingerling JR., Teo Y-Y., Haines JL., Wolfs RCW., Lemij HG., Tai E-S., Jansonius NM., Jonas JB., Cheng C-Y., Aung T., Viswanathan AC., Klaver CCW., Craig JE., Macgregor S., Mackey DA., Lotery AJ., Stefansson K., Bergen AAB., Young TL., Wiggs JL., Pfeiffer N., Wong T-Y., Pasquale LR., Hewitt AW., van Duijn CM., Hammond CJ.
AbstractGlaucoma 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.