Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

Milly S. Tedja, Robert Wojciechowski, Pirro G. Hysi, Nicholas Eriksson, Nicholas A. Furlotte, Virginie J.M. Verhoeven, Adriana I. Iglesias, Magda A. Meester-Smoor, Stuart W. Tompson, Qiao Fan, Anthony P. Khawaja, Ching Yu Cheng, René Höhn, Kenji Yamashiro, Adam Wenocur, Clare Grazal, Toomas Haller, Andres Metspalu, Juho Wedenoja, Jost B. JonasYa Xing Wang, Jing Xie, Paul Mitchell, Paul J. Foster, Barbara E.K. Klein, Ronald Klein, Andrew D. Paterson, S. Mohsen Hosseini, Rupal L. Shah, Cathy Williams, Yik Ying Teo, Yih Chung Tham, Preeti Gupta, Wanting Zhao, Yuan Shi, Woei Yuh Saw, E. Shyong Tai, Xue Ling Sim, Jennifer E. Huffman, Ozren Polašek, Caroline Hayward, Goran Bencic, Igor Rudan, James F. Wilson, Tin Aung, Amutha B. Veluchamy, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Peng Chen, Wei Chen, Emily Chew, Margaret M. Deangelis, Xiaohu Ding, Angela Döring, David M. Evans, Sheng Feng, Brian Fleck, Rhys D. Fogarty, Jeremy R. Fondran, Maurizio Fossarello, Xiaobo Guo, Annet E.G. Haarman, Mingguang He, Laura D. Howe, Sarayut Janmahasatian, Vishal Jhanji, Mika Kähönen, Jaakko Kaprio, John P. Kemp, Kay Tee Khaw, Chiea Chuen Khor, Eva Krapohl

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127 Citations (Scopus)


Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.
Original languageEnglish
Pages (from-to)834-848
Number of pages15
JournalNature Genetics
Issue number6
Publication statusPublished - 1 Jun 2018
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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