TY - JOUR T1 - Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. JF - Nat Genet Y1 - 2018 A1 - Tedja, Milly S A1 - Wojciechowski, Robert A1 - Hysi, Pirro G A1 - Eriksson, Nicholas A1 - Furlotte, Nicholas A A1 - Verhoeven, Virginie J M A1 - Iglesias, Adriana I A1 - Meester-Smoor, Magda A A1 - Tompson, Stuart W A1 - Fan, Qiao A1 - Khawaja, Anthony P A1 - Cheng, Ching-Yu A1 - Höhn, René A1 - Yamashiro, Kenji A1 - Wenocur, Adam A1 - Grazal, Clare A1 - Haller, Toomas A1 - Metspalu, Andres A1 - Wedenoja, Juho A1 - Jonas, Jost B A1 - Wang, Ya Xing A1 - Xie, Jing A1 - Mitchell, Paul A1 - Foster, Paul J A1 - Klein, Barbara E K A1 - Klein, Ronald A1 - Paterson, Andrew D A1 - Hosseini, S Mohsen A1 - Shah, Rupal L A1 - Williams, Cathy A1 - Teo, Yik Ying A1 - Tham, Yih Chung A1 - Gupta, Preeti A1 - Zhao, Wanting A1 - Shi, Yuan A1 - Saw, Woei-Yuh A1 - Tai, E-Shyong A1 - Sim, Xue Ling A1 - Huffman, Jennifer E A1 - Polasek, Ozren A1 - Hayward, Caroline A1 - Bencic, Goran A1 - Rudan, Igor A1 - Wilson, James F A1 - Joshi, Peter K A1 - Tsujikawa, Akitaka A1 - Matsuda, Fumihiko A1 - Whisenhunt, Kristina N A1 - Zeller, Tanja A1 - van der Spek, Peter J A1 - Haak, Roxanna A1 - Meijers-Heijboer, Hanne A1 - van Leeuwen, Elisabeth M A1 - Iyengar, Sudha K A1 - Lass, Jonathan H A1 - Hofman, Albert A1 - Rivadeneira, Fernando A1 - Uitterlinden, André G A1 - Vingerling, Johannes R A1 - Lehtimäki, Terho A1 - Raitakari, Olli T A1 - Biino, Ginevra A1 - Concas, Maria Pina A1 - Schwantes-An, Tae-Hwi A1 - Igo, Robert P A1 - Cuellar-Partida, Gabriel A1 - Martin, Nicholas G A1 - Craig, Jamie E A1 - Gharahkhani, Puya A1 - Williams, Katie M A1 - Nag, Abhishek A1 - Rahi, Jugnoo S A1 - Cumberland, Phillippa M A1 - Delcourt, Cécile A1 - Bellenguez, Céline A1 - Ried, Janina S A1 - Bergen, Arthur A A1 - Meitinger, Thomas A1 - Gieger, Christian A1 - Wong, Tien Yin A1 - Hewitt, Alex W A1 - Mackey, David A A1 - Simpson, Claire L A1 - Pfeiffer, Norbert A1 - Pärssinen, Olavi A1 - Baird, Paul N A1 - Vitart, Veronique A1 - Amin, Najaf A1 - van Duijn, Cornelia M A1 - Bailey-Wilson, Joan E A1 - Young, Terri L A1 - Saw, Seang-Mei A1 - Stambolian, Dwight A1 - MacGregor, Stuart A1 - Guggenheim, Jeremy A A1 - Tung, Joyce Y A1 - Hammond, Christopher J A1 - Klaver, Caroline C W AB -

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.

VL - 50 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29808027?dopt=Abstract ER -