A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease

Author:

Gharahkhani PuyaORCID,Jorgenson Eric,Hysi Pirro,Khawaja Anthony P.,Pendergrass Sarah,Han Xikun,Ong Jue Sheng,Hewitt Alex W.,Segre Ayellet,Igo Robert P.,Choquet Helene,Qassim Ayub,Josyula Navya S,Cooke Bailey Jessica N.,Bonnemaijer Pieter,Iglesias Adriana,Siggs Owen M.ORCID,Young Terri,Vitart Veronique,Thiadens Alberta A.H.J.,Karjalainen Juha,Uebe Steffen,Melles Ronald B.,Nair K. Saidas,Luben Robert,Simcoe Mark,Amersinghe Nishani,Cree Angela J.,Hohn Rene,Poplawski Alicia,Chen (CUHK) Li Jia,Cheng Ching-Yu,Vithana Eranga Nishanthie,Tamiya Gen,Shiga Yukihiro,Yamamoto Masayuki,Nakazawa Toru,Rouhana John,Currant Hannah,Birney Ewan,Wang Xin,Auton Adam,Ashaye Adeyinka,Olawoye Olusola,Williams Susan E.,Akafo Stephen,Ramsay Michele,Hashimoto Kazuki,Kamatani Yoichito,Akiama Masato,Momozawa Yukihide,Foster Paul J.,Khaw Peng T.,Morgan James E.,Strouthidis Nicholas G.,Kraft Peter,Kang Jae Hee,Pui Pang (CUHK) Calvin Chi,Pasutto Francesca,Mitchell Paul,Lotery Andrew J.,Palotie Aarno,van Duijn Cornelia,Haines Jonathan,Hammond Chris,Pasquale Louis R.,Klaver Caroline C.W.,Hauser Michael,Khor Chiea Chuen,Mackey David A.,Kubo Michiaki,Aung Tin,Craig Jamie,MacGregor Stuart,Wiggs Janey, , , , , , ,

Abstract

AbstractWe conducted a large multi-ethnic meta-analysis of genome-wide association studies for primary open-angle glaucoma (POAG) on a total of 34,179 cases vs 349,321 controls, and identified 127 independent risk loci, almost doubling the number of known loci for POAG. The majority of loci have broadly consistent effect across European, Asian and African ancestries. We identify a link, both genome-wide and at specific loci, between POAG and Alzheimer’s disease. Gene expression data and bioinformatic functional analyses provide further support for the functional relevance of the POAG risk genes. Several drug compounds target these risk genes and may be potential candidates for developing novel POAG treatments.

Publisher

Cold Spring Harbor Laboratory

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