TY - JOUR
T1 - Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error
AU - The CREAM Consortium
AU - the 23 and Me Research Team
AU - UK Biobank Eye and Vision Consortium
AU - Tedja, Milly S.
AU - Wojciechowski, Robert
AU - Hysi, Pirro G.
AU - Eriksson, Nicholas
AU - Furlotte, Nicholas A.
AU - Verhoeven, Virginie J.M.
AU - Iglesias, Adriana I.
AU - Meester-Smoor, Magda A.
AU - Tompson, Stuart W.
AU - Fan, Qiao
AU - Khawaja, Anthony P.
AU - Cheng, Ching Yu
AU - Höhn, René
AU - Yamashiro, Kenji
AU - Wenocur, Adam
AU - Grazal, Clare
AU - Haller, Toomas
AU - Metspalu, Andres
AU - Wedenoja, Juho
AU - Jonas, Jost B.
AU - Wang, Ya Xing
AU - Xie, Jing
AU - Mitchell, Paul
AU - Foster, Paul J.
AU - Klein, Barbara E.K.
AU - Klein, Ronald
AU - Paterson, Andrew D.
AU - Hosseini, S. Mohsen
AU - Shah, Rupal L.
AU - Williams, Cathy
AU - Teo, Yik Ying
AU - Tham, Yih Chung
AU - Gupta, Preeti
AU - Zhao, Wanting
AU - Shi, Yuan
AU - Saw, Woei Yuh
AU - Tai, E. Shyong
AU - Sim, Xue Ling
AU - Evans, David M.
AU - Howe, Laura D.
AU - Kemp, John P.
AU - McMahon, George
AU - Pourcain, Beate St
AU - Timpson, Nicholas J.
AU - Wang, Jie Jin
AU - Bishop, Paul N.
AU - Dick, Andrew D.
AU - Steel, David H.W.
AU - Williams, Katie M.
AU - Guggenheim, Jeremy A.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85047796358&partnerID=8YFLogxK
U2 - 10.1038/s41588-018-0127-7
DO - 10.1038/s41588-018-0127-7
M3 - Article (Academic Journal)
C2 - 29808027
AN - SCOPUS:85047796358
SN - 1061-4036
VL - 50
SP - 834
EP - 848
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -
