Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. : Nat Genet
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Tedja, M. S. | Wojciechowski, R. | Hysi, P. G. | Eriksson, N. | Furlotte, N. A. | Verhoeven, V. J. M. | Iglesias, A. I. | Meester-Smoor, M. A. | Tompson, S. W. | Fan, Q. | Khawaja, A. P. | Cheng, C. Y. | Hohn, R. | Yamashiro, K. | Wenocur, A. | Grazal, C. | Haller, T. | Metspalu, A. | Wedenoja, J. | Jonas, J. B. | Wang, Y. X. | Xie, J. | Mitchell, P. | Foster, P. J. | Klein, B. E. K. | Klein, R. | Paterson, A. D. | Hosseini, S. M. | Shah, R. L. | Williams, C. | Teo, Y. Y. | Tham, Y. C. | Gupta, P. | Zhao, W. | Shi, Y. | Saw, W. Y. | Tai, E. S. | Sim, X. L. | Huffman, J. E. | Polasek, O. | Hayward, C. | Bencic, G. | Rudan, I. | Wilson, J. F. | Joshi, P. K. | Tsujikawa, A. | Matsuda, F. | Whisenhunt, K. N. | Zeller, T. | van Der Spek, P. J. | Haak, R. | Meijers-Heijboer, H. | van Leeuwen, E. M. | Iyengar, S. K. | Lass, J. H. | Hofman, A. | Rivadeneira, F. | Uitterlinden, A. G. | Vingerling, J. R. | Lehtimaki, T. | Raitakari, O. T. | Biino, G. | Concas, M. P. | Schwantes-An, T. H. | Igo, R. P., Jr. | Cuellar-Partida, G. | Martin, N. G. | Craig, J. E. | Gharahkhani, P. | Williams, K. M. | Nag, A. | Rahi, J. S. | Cumberland, P. M. | Delcourt, Cécile | Bellenguez, C. | Ried, J. S. | Bergen, A. A. | Meitinger, T. | Gieger, C. | Wong, T. Y. | Hewitt, A. W. | Mackey, D. A. | Simpson, C. L. | Pfeiffer, N. | Parssinen, O. | Baird, P. N. | Vitart, V. | Amin, N. | van Duijn, C. M. | Bailey-Wilson, J. E. | Young, T. L. | Saw, S. M. | Stambolian, D. | Macgregor, S. | Guggenheim, J. A. | Tung, J. Y. | Hammond, C. J. | Klaver, C. C. W.
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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.
