학술논문
Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error
Document Type
Article
Author
Tedja, Milly; Wojciechowski, Robert; Hysi, Pirro; Eriksson, Nicholas; Furlotte, Nicholas; Verhoeven, Virginie; Iglesias, Adriana; Meester-Smoor, Magda; Tompson, Stuart; Fan, Qiao; Khawaja, Anthony; Cheng, Ching-Yu; Höhn, René; Yamashiro, Kenji; Wenocur, Adam; Grazal, Clare; Haller, Toomas; Metspalu, Andres; Wedenoja, Juho; Jonas, Jost; Wang, Ya; Xie, Jing; Mitchell, Paul; Foster, Paul; Klein, Barbara; Klein, Ronald; Paterson, Andrew; Hosseini, S.; Shah, Rupal; Williams, Cathy; Teo, Yik; Tham, Yih; Gupta, Preeti; Zhao, Wanting; Shi, Yuan; Saw, Woei-Yuh; Tai, E-Shyong; Sim, Xue; Huffman, Jennifer; Polašek, Ozren; Hayward, Caroline; Bencic, Goran; Rudan, Igor; Wilson, James; Joshi, Peter; Tsujikawa, Akitaka; Matsuda, Fumihiko; Whisenhunt, Kristina; Zeller, Tanja; Spek, Peter; Haak, Roxanna; Meijers-Heijboer, Hanne; van Leeuwen, Elisabeth; Iyengar, Sudha; Lass, Jonathan; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André; Vingerling, Johannes; Lehtimäki, Terho; Raitakari, Olli; Biino, Ginevra; Concas, Maria; Schwantes-An, Tae-Hwi; Igo, Robert; Cuellar-Partida, Gabriel; Martin, Nicholas; Craig, Jamie; Gharahkhani, Puya; Williams, Katie; Nag, Abhishek; Rahi, Jugnoo; Cumberland, Phillippa; Delcourt, Cécile; Bellenguez, Céline; Ried, Janina; Bergen, Arthur; Meitinger, Thomas; Gieger, Christian; Wong, Tien; Hewitt, Alex; Mackey, David; Simpson, Claire; Pfeiffer, Norbert; Pärssinen, Olavi; Baird, Paul; Vitart, Veronique; Amin, Najaf; Duijn, Cornelia; Bailey-Wilson, Joan; Young, Terri; Saw, Seang-Mei; Stambolian, Dwight; MacGregor, Stuart; Guggenheim, Jeremy; Tung, Joyce; Hammond, Christopher; Klaver, Caroline
Source
Nature Genetics; June 2018, Vol. 50 Issue: 6 p834-848, 15p
Subject
Language
ISSN
10614036; 15461718
Abstract
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. Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.