Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

Ekaterina Yonova-Doing; Wanting Zhao; Robert P. Igo; Chaolong Wang; Periasamy Sundaresan; Kristine E. Lee; Gyungah R. Jun; Alexessander Couto Alves; Xiaoran Chai; Anita S.Y. Chan; Mei Chin Lee; Allan Fong; Ava G. Tan; Chiea Chuen Khor; Emily Y. Chew; Pirro G. Hysi; Qiao Fan; Jacqueline Chua; Jaeyoon Chung; Jiemin Liao; Johanna M. Colijn; Kathryn P. Burdon; Lars G. Fritsche; Maria K. Swift; Maryam H. Hilmy; Miao Ling Chee; Milly Tedja; Pieter W.M. Bonnemaijer; Preeti Gupta; Queenie S. Tan; Zheng Li; Eranga N. Vithana; Ravilla D. Ravindran; Soon Phaik Chee; Yuan Shi; Wenting Liu; Xinyi Su; Xueling Sim; Yang Shen; Ya Xing Wang; Hengtong Li; Yih Chung Tham; Yik Ying Teo; Tin Aung; Kerrin S. Small; Paul Mitchell; Jost B. Jonas; Tien Yin Wong; Astrid E. Fletcher; Caroline C.W. Klaver; Barbara E.K. Klein; Jie Jin Wang; Sudha K. Iyengar; Christopher J. Hammond; Ching Yu Cheng

doi:10.1038/s42003-020-01421-2

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

Ekaterina Yonova-Doing, Wanting Zhao, Robert P. Igo, Chaolong Wang, Periasamy Sundaresan, Kristine E. Lee, Gyungah R. Jun, Alexessander Couto Alves, Xiaoran Chai, Anita S.Y. Chan, Mei Chin Lee, Allan Fong, Ava G. Tan, Chiea Chuen Khor, Emily Y. Chew, Pirro G. Hysi, Qiao Fan, Jacqueline Chua, Jaeyoon Chung, Jiemin LiaoJohanna M. Colijn, Kathryn P. Burdon, Lars G. Fritsche, Maria K. Swift, Maryam H. Hilmy, Miao Ling Chee, Milly Tedja, Pieter W.M. Bonnemaijer, Preeti Gupta, Queenie S. Tan, Zheng Li, Eranga N. Vithana, Ravilla D. Ravindran, Soon Phaik Chee, Yuan Shi, Wenting Liu, Xinyi Su, Xueling Sim, Yang Shen, Ya Xing Wang, Hengtong Li, Yih Chung Tham, Yik Ying Teo, Tin Aung, Kerrin S. Small, Paul Mitchell, Jost B. Jonas, Tien Yin Wong, Astrid E. Fletcher, Caroline C.W. Klaver, Barbara E.K. Klein, Jie Jin Wang, Sudha K. Iyengar, Christopher J. Hammond^*, Ching Yu Cheng

^*Corresponding author for this work

Ophthalmology

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h² = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10⁻¹⁶) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10⁻¹⁹), TMPRSS5 (rs4936279, P = 2.5 × 10⁻¹⁰), LINC01412 (rs16823886, P = 1.3 × 10⁻⁹), GLTSCR1 (rs1005911, P = 9.8 × 10⁻⁹), and COMMD1 (rs62149908, P = 1.2 × 10⁻⁸). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

Original language	English
Article number	755
Journal	Communications Biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-01421-2
Publication status	Published - Dec 2020

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Yonova-Doing, E., Zhao, W., Igo, R. P., Wang, C., Sundaresan, P., Lee, K. E., Jun, G. R., Alves, A. C., Chai, X., Chan, A. S. Y., Lee, M. C., Fong, A., Tan, A. G., Khor, C. C., Chew, E. Y., Hysi, P. G., Fan, Q., Chua, J., Chung, J., ... Cheng, C. Y. (2020). Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract. Communications Biology, 3(1), Article 755. https://doi.org/10.1038/s42003-020-01421-2

@article{5a78ac6b0b5e426589b171b34030fa10,

title = "Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract",

abstract = "Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.",

author = "Ekaterina Yonova-Doing and Wanting Zhao and Igo, {Robert P.} and Chaolong Wang and Periasamy Sundaresan and Lee, {Kristine E.} and Jun, {Gyungah R.} and Alves, {Alexessander Couto} and Xiaoran Chai and Chan, {Anita S.Y.} and Lee, {Mei Chin} and Allan Fong and Tan, {Ava G.} and Khor, {Chiea Chuen} and Chew, {Emily Y.} and Hysi, {Pirro G.} and Qiao Fan and Jacqueline Chua and Jaeyoon Chung and Jiemin Liao and Colijn, {Johanna M.} and Burdon, {Kathryn P.} and Fritsche, {Lars G.} and Swift, {Maria K.} and Hilmy, {Maryam H.} and Chee, {Miao Ling} and Milly Tedja and Bonnemaijer, {Pieter W.M.} and Preeti Gupta and Tan, {Queenie S.} and Zheng Li and Vithana, {Eranga N.} and Ravindran, {Ravilla D.} and Chee, {Soon Phaik} and Yuan Shi and Wenting Liu and Xinyi Su and Xueling Sim and Yang Shen and Wang, {Ya Xing} and Hengtong Li and Tham, {Yih Chung} and Teo, {Yik Ying} and Tin Aung and Small, {Kerrin S.} and Paul Mitchell and Jonas, {Jost B.} and Wong, {Tien Yin} and Fletcher, {Astrid E.} and Klaver, {Caroline C.W.} and Klein, {Barbara E.K.} and Wang, {Jie Jin} and Iyengar, {Sudha K.} and Hammond, {Christopher J.} and Cheng, {Ching Yu}",

year = "2020",

month = dec,

doi = "10.1038/s42003-020-01421-2",

language = "English",

volume = "3",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Yonova-Doing, E, Zhao, W, Igo, RP, Wang, C, Sundaresan, P, Lee, KE, Jun, GR, Alves, AC, Chai, X, Chan, ASY, Lee, MC, Fong, A, Tan, AG, Khor, CC, Chew, EY, Hysi, PG, Fan, Q, Chua, J, Chung, J, Liao, J, Colijn, JM, Burdon, KP, Fritsche, LG, Swift, MK, Hilmy, MH, Chee, ML, Tedja, M, Bonnemaijer, PWM, Gupta, P, Tan, QS, Li, Z, Vithana, EN, Ravindran, RD, Chee, SP, Shi, Y, Liu, W, Su, X, Sim, X, Shen, Y, Wang, YX, Li, H, Tham, YC, Teo, YY, Aung, T, Small, KS, Mitchell, P, Jonas, JB, Wong, TY, Fletcher, AE, Klaver, CCW, Klein, BEK, Wang, JJ, Iyengar, SK, Hammond, CJ & Cheng, CY 2020, 'Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract', Communications Biology, vol. 3, no. 1, 755. https://doi.org/10.1038/s42003-020-01421-2

TY - JOUR

T1 - Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

AU - Yonova-Doing, Ekaterina

AU - Zhao, Wanting

AU - Igo, Robert P.

AU - Wang, Chaolong

AU - Sundaresan, Periasamy

AU - Lee, Kristine E.

AU - Jun, Gyungah R.

AU - Alves, Alexessander Couto

AU - Chai, Xiaoran

AU - Chan, Anita S.Y.

AU - Lee, Mei Chin

AU - Fong, Allan

AU - Tan, Ava G.

AU - Khor, Chiea Chuen

AU - Chew, Emily Y.

AU - Hysi, Pirro G.

AU - Fan, Qiao

AU - Chua, Jacqueline

AU - Chung, Jaeyoon

AU - Liao, Jiemin

AU - Colijn, Johanna M.

AU - Burdon, Kathryn P.

AU - Fritsche, Lars G.

AU - Swift, Maria K.

AU - Hilmy, Maryam H.

AU - Chee, Miao Ling

AU - Tedja, Milly

AU - Bonnemaijer, Pieter W.M.

AU - Gupta, Preeti

AU - Tan, Queenie S.

AU - Li, Zheng

AU - Vithana, Eranga N.

AU - Ravindran, Ravilla D.

AU - Chee, Soon Phaik

AU - Shi, Yuan

AU - Liu, Wenting

AU - Su, Xinyi

AU - Sim, Xueling

AU - Shen, Yang

AU - Wang, Ya Xing

AU - Li, Hengtong

AU - Tham, Yih Chung

AU - Teo, Yik Ying

AU - Aung, Tin

AU - Small, Kerrin S.

AU - Mitchell, Paul

AU - Jonas, Jost B.

AU - Wong, Tien Yin

AU - Fletcher, Astrid E.

AU - Klaver, Caroline C.W.

AU - Klein, Barbara E.K.

AU - Wang, Jie Jin

AU - Iyengar, Sudha K.

AU - Hammond, Christopher J.

AU - Cheng, Ching Yu

PY - 2020/12

Y1 - 2020/12

N2 - Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

AB - Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

UR - http://www.scopus.com/inward/record.url?scp=85097438096&partnerID=8YFLogxK

U2 - 10.1038/s42003-020-01421-2

DO - 10.1038/s42003-020-01421-2

M3 - Article

AN - SCOPUS:85097438096

SN - 2399-3642

VL - 3

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 755

ER -

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

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