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

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.

%B Nat Genet %V 50 %P 834-848 %8 2018 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/29808027?dopt=Abstract %R 10.1038/s41588-018-0127-7