Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

Milly S. Tedja, Robert Wojciechowski, Pirro G. Hysi, Nicholas Eriksson, Nicholas A. Furlotte, Virginie J.M. Verhoeven, Adriana I. Iglesias, Magda A. Meester-Smoor, Stuart W. Tompson, Qiao Fan, Anthony P. Khawaja, Ching Yu Cheng, René Höhn, Kenji Yamashiro, Adam Wenocur, Clare Grazal, Toomas Haller, Andres Metspalu, Juho Wedenoja, Jost B. Jonas & 33 others Ya Xing Wang, Jing Xie, Paul Mitchell, Paul J. Foster, Barbara E.K. Klein, Ronald Klein, Andrew D. Paterson, S. Mohsen Hosseini, Rupal L. Shah, Cathy Williams, Yik Ying Teo, Yih Chung Tham, Preeti Gupta, Wanting Zhao, Yuan Shi, Woei Yuh Saw, E. Shyong Tai, Xue Ling Sim, Jennifer E. Huffman, Ozren Polašek, Caroline Hayward, Goran Bencic, Igor Rudan, James F. Wilson, Tin Aung, Amutha B. Veluchamy, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Rhys D. Fogarty, CREAM, 23andMe Research Team, UK Biobank Eye and Vision Consortium

Research output: Contribution to journalArticle

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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.

LanguageEnglish
Pages834-848
Number of pages15
JournalNature Genetics
Volume50
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Cite this

Tedja, M. S., Wojciechowski, R., Hysi, P. G., Eriksson, N., Furlotte, N. A., Verhoeven, V. J. M., ... UK Biobank Eye and Vision Consortium (2018). Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nature Genetics, 50(6), 834-848. https://doi.org/10.1038/s41588-018-0127-7
Tedja, Milly S. ; Wojciechowski, Robert ; Hysi, Pirro G. ; Eriksson, Nicholas ; Furlotte, Nicholas A. ; Verhoeven, Virginie J.M. ; Iglesias, Adriana I. ; Meester-Smoor, Magda A. ; Tompson, Stuart W. ; Fan, Qiao ; Khawaja, Anthony P. ; Cheng, Ching Yu ; Höhn, René ; Yamashiro, Kenji ; Wenocur, Adam ; Grazal, Clare ; Haller, Toomas ; Metspalu, Andres ; Wedenoja, Juho ; Jonas, Jost B. ; Wang, Ya Xing ; Xie, Jing ; Mitchell, Paul ; Foster, Paul J. ; Klein, Barbara E.K. ; Klein, Ronald ; Paterson, Andrew D. ; Hosseini, S. Mohsen ; Shah, Rupal L. ; Williams, Cathy ; Teo, Yik Ying ; Tham, Yih Chung ; Gupta, Preeti ; Zhao, Wanting ; Shi, Yuan ; Saw, Woei Yuh ; Tai, E. Shyong ; Sim, Xue Ling ; Huffman, Jennifer E. ; Polašek, Ozren ; Hayward, Caroline ; Bencic, Goran ; Rudan, Igor ; Wilson, James F. ; Aung, Tin ; Veluchamy, Amutha B. ; Burdon, Kathryn P. ; Campbell, Harry ; Chen, Li Jia ; Fogarty, Rhys D. ; CREAM ; 23andMe Research Team ; UK Biobank Eye and Vision Consortium. / Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. In: Nature Genetics. 2018 ; Vol. 50, No. 6. pp. 834-848.
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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.",
author = "Tedja, {Milly S.} and Robert Wojciechowski and Hysi, {Pirro G.} and Nicholas Eriksson and Furlotte, {Nicholas A.} and Verhoeven, {Virginie J.M.} and Iglesias, {Adriana I.} and Meester-Smoor, {Magda A.} and Tompson, {Stuart W.} and Qiao Fan and Khawaja, {Anthony P.} and Cheng, {Ching Yu} and Ren{\'e} H{\"o}hn and Kenji Yamashiro and Adam Wenocur and Clare Grazal and Toomas Haller and Andres Metspalu and Juho Wedenoja and Jonas, {Jost B.} and Wang, {Ya Xing} and Jing Xie and Paul Mitchell and Foster, {Paul J.} and Klein, {Barbara E.K.} and Ronald Klein and Paterson, {Andrew D.} and Hosseini, {S. Mohsen} and Shah, {Rupal L.} and Cathy Williams and Teo, {Yik Ying} and Tham, {Yih Chung} and Preeti Gupta and Wanting Zhao and Yuan Shi and Saw, {Woei Yuh} and Tai, {E. Shyong} and Sim, {Xue Ling} and Huffman, {Jennifer E.} and Ozren Polašek and Caroline Hayward and Goran Bencic and Igor Rudan and Wilson, {James F.} and Tin Aung and Veluchamy, {Amutha B.} and Burdon, {Kathryn P.} and Harry Campbell and Chen, {Li Jia} and Fogarty, {Rhys D.} and CREAM and {23andMe Research Team} and {UK Biobank Eye and Vision Consortium}",
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Tedja, MS, Wojciechowski, R, Hysi, PG, Eriksson, N, Furlotte, NA, Verhoeven, VJM, Iglesias, AI, Meester-Smoor, MA, Tompson, SW, Fan, Q, Khawaja, AP, Cheng, CY, Höhn, R, Yamashiro, K, Wenocur, A, Grazal, C, Haller, T, Metspalu, A, Wedenoja, J, Jonas, JB, Wang, YX, Xie, J, Mitchell, P, Foster, PJ, Klein, BEK, Klein, R, Paterson, AD, Hosseini, SM, Shah, RL, Williams, C, Teo, YY, Tham, YC, Gupta, P, Zhao, W, Shi, Y, Saw, WY, Tai, ES, Sim, XL, Huffman, JE, Polašek, O, Hayward, C, Bencic, G, Rudan, I, Wilson, JF, Aung, T, Veluchamy, AB, Burdon, KP, Campbell, H, Chen, LJ, Fogarty, RD, CREAM, 23andMe Research Team & UK Biobank Eye and Vision Consortium 2018, 'Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error', Nature Genetics, vol. 50, no. 6, pp. 834-848. https://doi.org/10.1038/s41588-018-0127-7

Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. / Tedja, Milly S.; Wojciechowski, Robert; Hysi, Pirro G.; Eriksson, Nicholas; Furlotte, Nicholas A.; Verhoeven, Virginie J.M.; Iglesias, Adriana I.; Meester-Smoor, Magda A.; Tompson, Stuart W.; Fan, Qiao; Khawaja, Anthony P.; Cheng, Ching Yu; Höhn, René; Yamashiro, Kenji; Wenocur, Adam; Grazal, Clare; Haller, Toomas; Metspalu, Andres; Wedenoja, Juho; Jonas, Jost B.; Wang, Ya Xing; Xie, Jing; Mitchell, Paul; Foster, Paul J.; Klein, Barbara E.K.; Klein, Ronald; Paterson, Andrew D.; Hosseini, S. Mohsen; Shah, Rupal L.; Williams, Cathy; Teo, Yik Ying; Tham, Yih Chung; Gupta, Preeti; Zhao, Wanting; Shi, Yuan; Saw, Woei Yuh; Tai, E. Shyong; Sim, Xue Ling; Huffman, Jennifer E.; Polašek, Ozren; Hayward, Caroline; Bencic, Goran; Rudan, Igor; Wilson, James F.; Aung, Tin; Veluchamy, Amutha B.; Burdon, Kathryn P.; Campbell, Harry; Chen, Li Jia; Fogarty, Rhys D.; CREAM; 23andMe Research Team; UK Biobank Eye and Vision Consortium.

In: Nature Genetics, Vol. 50, No. 6, 01.06.2018, p. 834-848.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

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 - Huffman, Jennifer E.

AU - Polašek, Ozren

AU - Hayward, Caroline

AU - Bencic, Goran

AU - Rudan, Igor

AU - Wilson, James F.

AU - Aung, Tin

AU - Veluchamy, Amutha B.

AU - Burdon, Kathryn P.

AU - Campbell, Harry

AU - Chen, Li Jia

AU - Fogarty, Rhys D.

AU - CREAM

AU - 23andMe Research Team

AU - UK Biobank Eye and Vision Consortium

PY - 2018/6/1

Y1 - 2018/6/1

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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.

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Tedja MS, Wojciechowski R, Hysi PG, Eriksson N, Furlotte NA, Verhoeven VJM et al. Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nature Genetics. 2018 Jun 1;50(6):834-848. https://doi.org/10.1038/s41588-018-0127-7