Support our work
Decorative header background

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

Publication year 2018
Published in Nature Genetics
Authors 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 Jonas, Ya 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, Peter K Joshi, Akitaka Tsujikawa, Fumihiko Matsuda, Kristina N Whisenhunt, Tanja Zeller, P.J. Van der Spek, R. Haak, Hanne Meijers-Heijboer, E.M. van Leeuwen, Sudha K Iyengar, J.H. Lass, A. Hofman, F. Rivadeneira, A.G. Uitterlinden, J.R. Vingerling, T. Lehtimaki, O.T. Raitakari, G. Biino, M.P. Concas, T.H. Schwantes-An, R.P. Igo, G. Cuellar-Partida, N.G. Martin, J.E. Craig, P. Gharahkhani, K.M. Williams, A. Naq, J.S. Rahi, P.M. Cumberland, C. Delcourt, C. Bellenquez, J.S. Ried, A.A.B. Bergen, T. Meitinger, C. Gieger, T.Y. Wong, A.W. Hewitt, D.A. Mackey, C.L. Simpson, N. Pfeiffer, O. Parssinen, Paul N Baird, V. Vitart, N. Amin, C.M. Van Duijn, J.E. Bailey-Wilson, T.L. Young, S.M. Saw, D. Stambolian, S. MacGregor, J.A. Guggenheim, J.Y. Tung, C.J. Hammond, C.C.W. Klaver

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.

Support our work!

The Friends Foundation facilitates groundbreaking brain research. You can help us with that.

Support our work