Search

Your search keyword '"Wojciechowski R"' showing total 349 results
Start Over Author "Wojciechowski R"
349 results on '"Wojciechowski R"'

1. Examination of Wetting by Liquid Zinc of Steel Sheets Following Various Kinds of Abrasive Blasting

Author

Cecotka M., Dybowski K., Klimek L., Lipa S., Rylski A., Sankowski D., Wojciechowski R., and Bąkała M.

Subjects
abrasive blasting, dip zinc coating, surface preparation, wettability, Mining engineering. Metallurgy, TN1-997, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Abrasive blasting is one of the methods of surface working before hot-dip zinc-coating. It allows not only to remove products of corrosion from the surface, but it also affects the quality of the zinc coating applied later, thereby affecting wettability of surface being zinc-coated. The surface working can be done with different types of abrasive material.

Published
2016
Full Text
View/download PDF

2. Résultats de phase 2 d’efficacité et de tolérance jusqu’à 52 semaines du ianalumab, anti-BAFF récepteur (BAFF-R), chez les patients atteints de lupus érythémateux systémique (LES)

Author

Lazaro, E., primary, Agmon-Levin, N., additional, Ignatenko, S., additional, Gordienko, A., additional, Cortes-Hernandez, J., additional, Narongroeknawin, P., additional, Romanowska-Prochnicka, K., additional, Shen, N., additional, Ciferska, H., additional, Kodera, M., additional, Wei, C.C., additional, Leszczynski, P., additional, Lan, J.L., additional, Mysler, E., additional, Wojciechowski, R., additional, Tarr, T., additional, Vishneva, E., additional, Chen, Y.H., additional, Kaneko, Y., additional, Finzel, S., additional, Hoi, A., additional, Okada, M., additional, Koolvisoot, A., additional, Lee, S.S., additional, Dai, L., additional, Kaneko, H., additional, Rojkovich, B., additional, Sun, L., additional, Zotkin, E., additional, Magallares, B.P., additional, Sengupta, T., additional, Sips, C., additional, Oliver, S., additional, Avrameas, A., additional, and Lau, C., additional

Published
2024
Full Text
View/download PDF

3. POS0120 SAFETY AND EFFICACY OF SUBCUTANEOUS (S.C.) DOSE IANALUMAB (VAY736; ANTI-BAFFR mAb) ADMINISTERED MONTHLY OVER 28 WEEKS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Author

Cortés-Hernández, J., primary, Ignatenko, S., additional, Gordienko, A., additional, Agmon-Levin, N., additional, Narongroeknawin, P., additional, Romanowska -Prochnicka, K., additional, Shen, N., additional, Ciferská, H., additional, Kodera, M., additional, Wei, J. C. C., additional, Leszczynski, P., additional, Lan, J. L., additional, Wojciechowski, R., additional, Tarr, T., additional, Vishneva, E., additional, Chen, Y. H., additional, Kaneko, Y., additional, Finzel, S., additional, Hoi, A., additional, Okada, M., additional, Koolvisoot, A., additional, Lee, S. S., additional, Dai, L., additional, Kaneko, H., additional, Rojkovich, B., additional, Sun, L., additional, Zotkin, E., additional, Magallares, B., additional, Sengupta, T., additional, Sips, C., additional, and Oliver, S., additional

Published
2023
Full Text
View/download PDF

6. AB0198 EFFICACY AND SAFETY AFTER TRANSITION FROM REFERENCE ADALIMUMAB TO CT-P17 (ADALIMUMAB BIOSIMILAR: 100 MG/ML) IN COMPARISON WITH THE MAINTAINED TREATMENT (CT-P17 OR REFERENCE ADALIMUMAB) IN PATIENTS WITH MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS: 1-YEAR RESULT

Author

Furst, D., primary, Keystone, E., additional, Kay, J., additional, Jaworski, J., additional, Wojciechowski, R., additional, Wiland, P., additional, Dudek, A., additional, Krogulec, M., additional, Jeka, S., additional, Zielinska, A., additional, Trefler, J., additional, Bartnicka-Masłowska, K., additional, Krajewska-Wlodarczyk, M., additional, Klimiuk, P., additional, Lee, S. J., additional, Kim, S. H., additional, Bae, Y., additional, Yang, G., additional, Yoo, J., additional, and Kim, T., additional

Published
2021
Full Text
View/download PDF

7. Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia

Author

Hysi, P.G., Choquet, Helene, Khawaja, A.P., Wojciechowski, R., Tedja, M.S., Yin, Jie, Klaver, C.C.W., Jorgenson, E., Hammond, C.J., Hysi, P.G., Choquet, Helene, Khawaja, A.P., Wojciechowski, R., Tedja, M.S., Yin, Jie, Klaver, C.C.W., Jorgenson, E., and Hammond, C.J.

Abstract

Contains fulltext : 217764.pdf (Publisher’s version ) (Closed access)

Published
2020

8. Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression

Author

Craig, J.E., Han, X., Qassim, A., Hassall, M., Bailey, J.N., Kinzy, T.G., Khawaja, A.P., An, J., Marshall, H., Gharahkhani, P., Igo, R.P., Jr., Graham, S.L., Healey, P.R., Ong, J.S., Zhou, T., Siggs, O., Law, M.H., Souzeau, E., Ridge, B., Hysi, P.G., Burdon, K.P., Mills, R.A., Landers, J., Ruddle, J.B., Agar, A., Galanopoulos, A., White, A.J.R., Willoughby, C.E., Andrew, N.H., Best, S., Vincent, A.L., Goldberg, I., Radford-Smith, G., Martin, N.G., Montgomery, G.W., Vitart, V., Hoehn, R., Wojciechowski, R., Jonas, J.B., Aung, T., Pasquale, L.R., Cree, A.J., Sivaprasad, S., Vallabh, N.A., Viswanathan, A.C., Pasutto, F., Haines, J.L., Klaver, C.C.W., Duijn, C.M. van, Casson, R.J., Foster, P.J., Khaw, P.T., Hammond, C.J., Mackey, D.A., Mitchell, P., Lotery, A.J., Wiggs, J.L., Hewitt, A.W., MacGregor, S., Craig, J.E., Han, X., Qassim, A., Hassall, M., Bailey, J.N., Kinzy, T.G., Khawaja, A.P., An, J., Marshall, H., Gharahkhani, P., Igo, R.P., Jr., Graham, S.L., Healey, P.R., Ong, J.S., Zhou, T., Siggs, O., Law, M.H., Souzeau, E., Ridge, B., Hysi, P.G., Burdon, K.P., Mills, R.A., Landers, J., Ruddle, J.B., Agar, A., Galanopoulos, A., White, A.J.R., Willoughby, C.E., Andrew, N.H., Best, S., Vincent, A.L., Goldberg, I., Radford-Smith, G., Martin, N.G., Montgomery, G.W., Vitart, V., Hoehn, R., Wojciechowski, R., Jonas, J.B., Aung, T., Pasquale, L.R., Cree, A.J., Sivaprasad, S., Vallabh, N.A., Viswanathan, A.C., Pasutto, F., Haines, J.L., Klaver, C.C.W., Duijn, C.M. van, Casson, R.J., Foster, P.J., Khaw, P.T., Hammond, C.J., Mackey, D.A., Mitchell, P., Lotery, A.J., Wiggs, J.L., Hewitt, A.W., and MacGregor, S.

Abstract

Contains fulltext : 218893.pdf (Publisher’s version ) (Closed access), Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 x 10(-)(6)). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.

Published
2020

9. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author

Fan, Q. (Qiao), Pozarickij, A. (Alfred), Tan, N.Y.Q. (Nicholas Y. Q.), Guo, X. (Xiaobo), Verhoeven, V.J.M. (Virginie), Vitart, V. (Veronique), Guggenheim, J. (Jean), Miyake, M. (Masahiro), Tideman, J.W.L. (Willem), Khawaja, A.P. (Anthony), Zhang, L. (Liang), MacGregor, S. (Stuart), Höhn, R. (René), Chen, P. (Peng), Biino, G. (Ginevra), Wedenoja, J. (Juho), Saffari, S.E. (Seyed Ehsan), Tedja, M. (Milly), Xie, J. (Jing), Lanca, C. (Carla), Wang, Y.X. (Ya Xing), Sahebjada, S. (Srujana), Mazur, J. (Johanna), Mirshahi, A. (Alireza), Martin, N.G. (Nicholas), Yazar, S. (Seyhan), Pennell, C.E. (Craig), Yap, M.K.H. (Maurice K. H.), Haarman, A.E.G. (Annechien E. G.), Enthoven, C.A. (Clair A.), Polling, J.R. (Jan Roelof), Bailey-Wilson, J.E. (Joan E.), Veluchamy, A.B. (Amutha Barathi), Burdon, K.P. (Kathryn P.), Campbell, H. (Harry), Chen, L.J. (Li Jia), Chew, E.Y. (Emily Y.), Craig, J.E. (Jamie), Cumberland, P.M. (Phillippa M.), DeAngelis, M.M. (Margaret), Delcourt, C. (Cécile), Ding, X. (Xiaohu), Evans, D.M. (David M.), Gharahkhani, P. (Puya), Iglesias, A.I. (Adriana I.), Haller, T. (Toomas), Han, X. (Xikun), Hoang, Q. (Quan), Igo Jr., R.P. (Robert), Iyengar, S.K. (Sudha), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Klein, B.E. (Barbara E.), Klein, R. (Ronald), Lass Jr., J.H. (Jonathan), Lee, K. (Kris), Lehtimäki, T. (Terho), Lewis, D.D. (Deyana D.), Li, Q. (Qing), Li, S.-M. (Shi-Ming), Lyytikäinen, L.-P. (Leo-Pekka), Meguro, A. (Akira), Metspalu, A. (Andres), Middlebrooks, C.D. (Candace D.), Mizuki, N. (Nobuhisa), Musolf, A.M. (Anthony M.), Nickels, S. (Stefan), Oexle, K. (Konrad), Pang, C.P. (Chi Pui), Paterson, A.D. (Andrew), Rahi, J.S. (Jugnoo S.), Raitakari, O. (Olli), Rudan, I. (Igor), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wang, N. (Ningli), Bin Wei, W. (Wen), Williams, K.M. (Katie M.), Wilson, J.F. (James), Wojciechowski, R. (Robert), Yamashiro, K. (Kenji), Yam, J.C.S. (Jason C. S.), Zhou, X. (Xiangtian), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jenny H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Fruttiger, M. (Marcus), Gallacher, J. (John), Garway-Heath, D.F. (David F.), Gibson, J. (Jane), Gore, D. (Dan), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, S.P.T. (Sir Peng T.), Lascaratos, G. (Gerassimos), Lotery, A.J. (Andrew), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Viswanathan, A.C. (Ananth C.), Williams, K. (Katie), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Hewit, A.W. (Alex), Jaddoe, V.W.V. (Vincent), Duijn, C.M. (Cornelia) van, Hayward, C. (Caroline), Polasek, O. (Ozren), Tai, E.S. (Shyong), Yoshikatsu, H. (Hosoda), Hysi, P.G. (Pirro G.), Young, T.L. (Terri L.), Tsujikawa, A. (Akitaka), Wang, J.J. (Jie Jing), Mitchell, P. (Paul), Pfeiffer, A.F.H. (Andreas), Pärssinen, O. (Olavi), Foster, P.J. (Paul), Fossarello, M. (Maurizio), Yip, S.P. (Shea Ping), Williams, C. (Cathy), Hammond, C.J. (Christopher), Jonas, J.B., He, M. (Mingguang), Mackey, D.A. (David), Wong, T.-Y. (Tien-Yin), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Baird, P.N. (Paul), Cheng, C.-Y. (Ching-Yu), Fan, Q. (Qiao), Pozarickij, A. (Alfred), Tan, N.Y.Q. (Nicholas Y. Q.), Guo, X. (Xiaobo), Verhoeven, V.J.M. (Virginie), Vitart, V. (Veronique), Guggenheim, J. (Jean), Miyake, M. (Masahiro), Tideman, J.W.L. (Willem), Khawaja, A.P. (Anthony), Zhang, L. (Liang), MacGregor, S. (Stuart), Höhn, R. (René), Chen, P. (Peng), Biino, G. (Ginevra), Wedenoja, J. (Juho), Saffari, S.E. (Seyed Ehsan), Tedja, M. (Milly), Xie, J. (Jing), Lanca, C. (Carla), Wang, Y.X. (Ya Xing), Sahebjada, S. (Srujana), Mazur, J. (Johanna), Mirshahi, A. (Alireza), Martin, N.G. (Nicholas), Yazar, S. (Seyhan), Pennell, C.E. (Craig), Yap, M.K.H. (Maurice K. H.), Haarman, A.E.G. (Annechien E. G.), Enthoven, C.A. (Clair A.), Polling, J.R. (Jan Roelof), Bailey-Wilson, J.E. (Joan E.), Veluchamy, A.B. (Amutha Barathi), Burdon, K.P. (Kathryn P.), Campbell, H. (Harry), Chen, L.J. (Li Jia), Chew, E.Y. (Emily Y.), Craig, J.E. (Jamie), Cumberland, P.M. (Phillippa M.), DeAngelis, M.M. (Margaret), Delcourt, C. (Cécile), Ding, X. (Xiaohu), Evans, D.M. (David M.), Gharahkhani, P. (Puya), Iglesias, A.I. (Adriana I.), Haller, T. (Toomas), Han, X. (Xikun), Hoang, Q. (Quan), Igo Jr., R.P. (Robert), Iyengar, S.K. (Sudha), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Klein, B.E. (Barbara E.), Klein, R. (Ronald), Lass Jr., J.H. (Jonathan), Lee, K. (Kris), Lehtimäki, T. (Terho), Lewis, D.D. (Deyana D.), Li, Q. (Qing), Li, S.-M. (Shi-Ming), Lyytikäinen, L.-P. (Leo-Pekka), Meguro, A. (Akira), Metspalu, A. (Andres), Middlebrooks, C.D. (Candace D.), Mizuki, N. (Nobuhisa), Musolf, A.M. (Anthony M.), Nickels, S. (Stefan), Oexle, K. (Konrad), Pang, C.P. (Chi Pui), Paterson, A.D. (Andrew), Rahi, J.S. (Jugnoo S.), Raitakari, O. (Olli), Rudan, I. (Igor), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wang, N. (Ningli), Bin Wei, W. (Wen), Williams, K.M. (Katie M.), Wilson, J.F. (James), Wojciechowski, R. (Robert), Yamashiro, K. (Kenji), Yam, J.C.S. (Jason C. S.), Zhou, X. (Xiangtian), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jenny H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Fruttiger, M. (Marcus), Gallacher, J. (John), Garway-Heath, D.F. (David F.), Gibson, J. (Jane), Gore, D. (Dan), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, S.P.T. (Sir Peng T.), Lascaratos, G. (Gerassimos), Lotery, A.J. (Andrew), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Viswanathan, A.C. (Ananth C.), Williams, K. (Katie), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Hewit, A.W. (Alex), Jaddoe, V.W.V. (Vincent), Duijn, C.M. (Cornelia) van, Hayward, C. (Caroline), Polasek, O. (Ozren), Tai, E.S. (Shyong), Yoshikatsu, H. (Hosoda), Hysi, P.G. (Pirro G.), Young, T.L. (Terri L.), Tsujikawa, A. (Akitaka), Wang, J.J. (Jie Jing), Mitchell, P. (Paul), Pfeiffer, A.F.H. (Andreas), Pärssinen, O. (Olavi), Foster, P.J. (Paul), Fossarello, M. (Maurizio), Yip, S.P. (Shea Ping), Williams, C. (Cathy), Hammond, C.J. (Christopher), Jonas, J.B., He, M. (Mingguang), Mackey, D.A. (David), Wong, T.-Y. (Tien-Yin), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Baird, P.N. (Paul), and Cheng, C.-Y. (Ching-Yu)

Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Published
2020
Full Text
View/download PDF

10. Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression

Author

Craig, JE, Han, X, Qassim, A, Hassall, M, Bailey, JNC, Kinzy, TG, Khawaja, AP, An, J, Marshall, H, Gharahkhani, P, Igo, RP, Graham, SL, Healey, PR, Ong, J-S, Zhou, T, Siggs, O, Law, MH, Souzeau, E, Ridge, B, Hysi, PG, Burdon, KP, Mills, RA, Landers, J, Ruddle, JB, Agar, A, Galanopoulos, A, White, AJR, Willoughby, CE, Andrew, NH, Best, S, Vincent, AL, Goldberg, I, Radford-Smith, G, Martin, NG, Montgomery, GW, Vitart, V, Hoehn, R, Wojciechowski, R, Jonas, JB, Aung, T, Pasquale, LR, Cree, AJ, Sivaprasad, S, Vallabh, NA, Viswanathan, AC, Pasutto, F, Haines, JL, Klaver, CCW, van Duijn, CM, Casson, RJ, Foster, PJ, Khaw, PT, Hammond, CJ, Mackey, DA, Mitchell, P, Lotery, AJ, Wiggs, JL, Hewitt, AW, MacGregor, S, Craig, JE, Han, X, Qassim, A, Hassall, M, Bailey, JNC, Kinzy, TG, Khawaja, AP, An, J, Marshall, H, Gharahkhani, P, Igo, RP, Graham, SL, Healey, PR, Ong, J-S, Zhou, T, Siggs, O, Law, MH, Souzeau, E, Ridge, B, Hysi, PG, Burdon, KP, Mills, RA, Landers, J, Ruddle, JB, Agar, A, Galanopoulos, A, White, AJR, Willoughby, CE, Andrew, NH, Best, S, Vincent, AL, Goldberg, I, Radford-Smith, G, Martin, NG, Montgomery, GW, Vitart, V, Hoehn, R, Wojciechowski, R, Jonas, JB, Aung, T, Pasquale, LR, Cree, AJ, Sivaprasad, S, Vallabh, NA, Viswanathan, AC, Pasutto, F, Haines, JL, Klaver, CCW, van Duijn, CM, Casson, RJ, Foster, PJ, Khaw, PT, Hammond, CJ, Mackey, DA, Mitchell, P, Lotery, AJ, Wiggs, JL, Hewitt, AW, and MacGregor, S

Abstract

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10-6). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.

Published
2020

11. Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia

Author

Hysi, PG, Choquet, H, Khawaja, AP, Wojciechowski, R, Tedja, MS, Yin, J, Simcoe, MJ, Patasova, K, Mahroo, OA, Thai, KK, Cumberland, PM, Melles, RB, Verhoeven, VJM, Vitart, V, Segre, A, Stone, RA, Wareham, N, Hewitt, AW, Mackey, DA, Klaver, CCW, MacGregor, S, Khaw, PT, Foster, PJ, Guggenheim, JA, Rahi, JS, Jorgenson, E, Hammond, CJ, Hysi, PG, Choquet, H, Khawaja, AP, Wojciechowski, R, Tedja, MS, Yin, J, Simcoe, MJ, Patasova, K, Mahroo, OA, Thai, KK, Cumberland, PM, Melles, RB, Verhoeven, VJM, Vitart, V, Segre, A, Stone, RA, Wareham, N, Hewitt, AW, Mackey, DA, Klaver, CCW, MacGregor, S, Khaw, PT, Foster, PJ, Guggenheim, JA, Rahi, JS, Jorgenson, E, and Hammond, CJ

Abstract

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.

Published
2020

15. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, P.W.M. (Pieter), Leeuwen, E.M. (Elisabeth M. van), Iglesias, A.I. (Adriana I.), Gharahkhani, P. (Puya), Vitart, V. (Veronique), Khawaja, A.P. (Anthony), Simcoe, M. (Mark), Höhn, R. (René), Cree, A.J. (Angela), Igo Jr., R.P. (Robert), Burdon, K.P. (Kathryn P.), Craig, J.E. (Jamie), Hewit, A.W. (Alex), Jonas, J.B., Khor, C.-C. (Chiea-Cheun), Pasutto, F. (Francesca), Mackey, D.A. (David), Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C.P. (Chi Pui), Pasquale, L.R. (Louis R), Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Viswanathan, A.C. (Ananth C.), Wojciechowski, R. (Robert), Wong, T.Y. (Tien Yin), Young, T.L. (Terrri L), Zeller, T. (Tanja), Allingham, R.R. (R Rand), Budenz, D.L. (Donald L.), Bailey, J.C. (Jessica Cooke), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Kang, J.H. (Jae Hee), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak, M. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Wilmer, D.Z. (Don Zack), Atan, D. (Denize), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jennifer H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Foster, P.J. (Paul), Fruttiger, M. (Marcus), Gallacher, J.E.J. (John E. J.), Garway, D.F. (David F.), Gibson, J. (Jane), Dan Gore, (), Guggenheim, J. (Jean), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, P.T. (Peng T.), Lascaratos, G. (Gerassimos), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rahi, J.S. (Jugnoo S.), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Williams, C. (Cathy), Williams, K.M. (Katie M.), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Gerhold-Ay, A. (Aslihan), Nickels, S. (Stefan), Wilson, J.F. (James), Hayward, C. (Caroline), Boutin, T.S. (Thibaud S.), Polasek, O. (Ozren), Aung, T. (Tin), Khor, C.C., Amin, N. (Najaf), Lotery, A.J. (Andrew), Wiggs, J.L. (Janey L.), Cheng, C.-Y. (Ching-Yu), Hysi, P.G. (Pirro G.), Hammond, C.J. (Christopher), Thiadens, A.A.H.J. (Alberta), MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), Duijn, C.M. (Cornelia) van, Bonnemaijer, P.W.M. (Pieter), Leeuwen, E.M. (Elisabeth M. van), Iglesias, A.I. (Adriana I.), Gharahkhani, P. (Puya), Vitart, V. (Veronique), Khawaja, A.P. (Anthony), Simcoe, M. (Mark), Höhn, R. (René), Cree, A.J. (Angela), Igo Jr., R.P. (Robert), Burdon, K.P. (Kathryn P.), Craig, J.E. (Jamie), Hewit, A.W. (Alex), Jonas, J.B., Khor, C.-C. (Chiea-Cheun), Pasutto, F. (Francesca), Mackey, D.A. (David), Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C.P. (Chi Pui), Pasquale, L.R. (Louis R), Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Viswanathan, A.C. (Ananth C.), Wojciechowski, R. (Robert), Wong, T.Y. (Tien Yin), Young, T.L. (Terrri L), Zeller, T. (Tanja), Allingham, R.R. (R Rand), Budenz, D.L. (Donald L.), Bailey, J.C. (Jessica Cooke), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Kang, J.H. (Jae Hee), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak, M. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Wilmer, D.Z. (Don Zack), Atan, D. (Denize), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jennifer H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Foster, P.J. (Paul), Fruttiger, M. (Marcus), Gallacher, J.E.J. (John E. J.), Garway, D.F. (David F.), Gibson, J. (Jane), Dan Gore, (), Guggenheim, J. (Jean), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, P.T. (Peng T.), Lascaratos, G. (Gerassimos), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rahi, J.S. (Jugnoo S.), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Williams, C. (Cathy), Williams, K.M. (Katie M.), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Gerhold-Ay, A. (Aslihan), Nickels, S. (Stefan), Wilson, J.F. (James), Hayward, C. (Caroline), Boutin, T.S. (Thibaud S.), Polasek, O. (Ozren), Aung, T. (Tin), Khor, C.C., Amin, N. (Najaf), Lotery, A.J. (Andrew), Wiggs, J.L. (Janey L.), Cheng, C.-Y. (Ching-Yu), Hysi, P.G. (Pirro G.), Hammond, C.J. (Christopher), Thiadens, A.A.H.J. (Alberta), MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), and Duijn, C.M. (Cornelia) van

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019
Full Text
View/download PDF

16. IMI - Myopia Genetics Report

Author

Tedja, MS, Haarman, AEG, Meester-Smoor, MA, Kaprio, J, Mackey, DA, Guggenheim, JA, Hammond, CJ, Verhoeven, VJM, Klaver, CCW, Bailey-Wilson, JE, Baird, PN, Veluchamy, AB, Biino, G, Burdon, KP, Campbell, H, Chen, LJ, Cheng, C-Y, Chew, EY, Craig, JE, Cumberland, PM, Deangelis, MM, Delcourt, C, Ding, X, van Duijn, CM, Evans, DM, Fan, Q, Fossarello, M, Foster, PJ, Gharahkhani, P, Iglesias, AI, Guol, X, Haller, T, Han, X, Hayward, C, He, M, Hewitt, AW, Hoang, Q, Hysi, PG, Igo, RP, Iyengar, SK, Jonas, JB, Kahonen, M, Khawaja, AP, Klein, BE, Klein, R, Lass, JH, Lee, K, Lehtimaki, T, Lewis, D, Li, Q, Li, S-M, Lyytikainen, L-P, MacGregor, S, Martin, NG, Meguro, A, Metspalu, A, Middlebrooks, C, Miyake, M, Mizuki, N, Musolf, A, Nickels, S, Oexle, K, Pang, CP, Parssinen, O, Paterson, AD, Pfeiffer, N, Polasek, O, Rahi, JS, Raitakari, O, Rudan, I, Sahebjada, S, Saw, S-M, Stambolian, D, Simpson, CL, Tai, E-S, Tideman, JWL, Tsujikawa, A, Vitart, V, Wang, N, Wedenoja, J, Wei, WB, Williams, C, Williams, KM, Wilson, JF, Wojciechowski, R, Wang, YX, Yamashiro, K, Yam, JCS, Yap, MKH, Yazar, S, Yip, SP, Young, TL, Zhou, X, Tedja, MS, Haarman, AEG, Meester-Smoor, MA, Kaprio, J, Mackey, DA, Guggenheim, JA, Hammond, CJ, Verhoeven, VJM, Klaver, CCW, Bailey-Wilson, JE, Baird, PN, Veluchamy, AB, Biino, G, Burdon, KP, Campbell, H, Chen, LJ, Cheng, C-Y, Chew, EY, Craig, JE, Cumberland, PM, Deangelis, MM, Delcourt, C, Ding, X, van Duijn, CM, Evans, DM, Fan, Q, Fossarello, M, Foster, PJ, Gharahkhani, P, Iglesias, AI, Guol, X, Haller, T, Han, X, Hayward, C, He, M, Hewitt, AW, Hoang, Q, Hysi, PG, Igo, RP, Iyengar, SK, Jonas, JB, Kahonen, M, Khawaja, AP, Klein, BE, Klein, R, Lass, JH, Lee, K, Lehtimaki, T, Lewis, D, Li, Q, Li, S-M, Lyytikainen, L-P, MacGregor, S, Martin, NG, Meguro, A, Metspalu, A, Middlebrooks, C, Miyake, M, Mizuki, N, Musolf, A, Nickels, S, Oexle, K, Pang, CP, Parssinen, O, Paterson, AD, Pfeiffer, N, Polasek, O, Rahi, JS, Raitakari, O, Rudan, I, Sahebjada, S, Saw, S-M, Stambolian, D, Simpson, CL, Tai, E-S, Tideman, JWL, Tsujikawa, A, Vitart, V, Wang, N, Wedenoja, J, Wei, WB, Williams, C, Williams, KM, Wilson, JF, Wojciechowski, R, Wang, YX, Yamashiro, K, Yam, JCS, Yap, MKH, Yazar, S, Yip, SP, Young, TL, and Zhou, X

Abstract

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth.

Published
2019

17. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, PWM, van Leeuwen, EM, Iglesias, AI, Gharahkhani, P, Vitart, V, Khawaja, AP, Simcoe, M, Hoehn, R, Cree, AJ, Igo, RP, Burdon, KP, Craig, JE, Hewitt, AW, Jonas, J, Khor, C-C, Pasutto, F, Mackey, DA, Mitchell, P, Mishra, A, Pang, C, Pasquale, LR, Springelkamp, H, Thorleifsson, G, Thorsteinsdottir, U, Viswanathan, AC, Wojciechowski, R, Wong, T, Young, TL, Zeller, T, Atan, D, Aslam, T, Barman, SA, Barrett, JH, Bishop, P, Blows, P, Bunce, C, Carare, RO, Chakravarthy, U, Chan, M, Chua, SYL, Crabb, DP, Cumberland, PM, Day, A, Desai, P, Dhillon, B, Dick, AD, Egan, C, Ennis, S, Foster, P, Fruttiger, M, Gallacher, JEJ, Garway, DF, Gibson, J, Gore, D, Guggenheim, JA, Hardcastle, A, Harding, SP, Hogg, RE, Keane, PA, Khaw, PT, Lascaratos, G, Macgillivray, T, Mackie, S, Martin, K, McGaughey, M, McGuinness, B, Mckay, GJ, McKibbin, M, Mitry, D, Moore, T, Morgan, JE, Muthy, ZA, O'Sullivan, E, Owen, CG, Patel, P, Paterson, E, Peto, T, Petzold, A, Rahi, JS, Rudnikca, AR, Self, J, Sivaprasad, S, Steel, D, Stratton, I, Strouthidis, N, Sudlow, C, Thomas, D, Trucco, E, Tufail, A, Vernon, SA, Williams, C, Williams, K, Woodside, JV, Yates, MM, Yip, J, Zheng, Y, Allingham, R, Budenz, D, Bailey, JC, Fingert, J, Gaasterland, D, Gaasterland, T, Haines, JL, Hark, L, Hauser, M, Kang, JH, Kraft, P, Lee, R, Lichter, P, Liu, Y, Moroi, S, Pericak, M, Realini, A, Rhee, D, Richards, JR, Ritch, R, Scott, WK, Singh, K, Sit, A, Vollrath, D, Weinreb, R, Wollstein, G, Wilmer, DZ, Gerhold-Ay, A, Nickels, S, Wilson, JF, Hayward, C, Boutin, TS, Polasek, O, Aung, T, Khor, CC, Amin, N, Lotery, AJ, Wiggs, JL, Cheng, C-Y, Hysi, PG, Hammond, CJ, Thiadens, AAHJ, MacGregor, S, Klaver, CCW, van Duijn, CM, Bonnemaijer, PWM, van Leeuwen, EM, Iglesias, AI, Gharahkhani, P, Vitart, V, Khawaja, AP, Simcoe, M, Hoehn, R, Cree, AJ, Igo, RP, Burdon, KP, Craig, JE, Hewitt, AW, Jonas, J, Khor, C-C, Pasutto, F, Mackey, DA, Mitchell, P, Mishra, A, Pang, C, Pasquale, LR, Springelkamp, H, Thorleifsson, G, Thorsteinsdottir, U, Viswanathan, AC, Wojciechowski, R, Wong, T, Young, TL, Zeller, T, Atan, D, Aslam, T, Barman, SA, Barrett, JH, Bishop, P, Blows, P, Bunce, C, Carare, RO, Chakravarthy, U, Chan, M, Chua, SYL, Crabb, DP, Cumberland, PM, Day, A, Desai, P, Dhillon, B, Dick, AD, Egan, C, Ennis, S, Foster, P, Fruttiger, M, Gallacher, JEJ, Garway, DF, Gibson, J, Gore, D, Guggenheim, JA, Hardcastle, A, Harding, SP, Hogg, RE, Keane, PA, Khaw, PT, Lascaratos, G, Macgillivray, T, Mackie, S, Martin, K, McGaughey, M, McGuinness, B, Mckay, GJ, McKibbin, M, Mitry, D, Moore, T, Morgan, JE, Muthy, ZA, O'Sullivan, E, Owen, CG, Patel, P, Paterson, E, Peto, T, Petzold, A, Rahi, JS, Rudnikca, AR, Self, J, Sivaprasad, S, Steel, D, Stratton, I, Strouthidis, N, Sudlow, C, Thomas, D, Trucco, E, Tufail, A, Vernon, SA, Williams, C, Williams, K, Woodside, JV, Yates, MM, Yip, J, Zheng, Y, Allingham, R, Budenz, D, Bailey, JC, Fingert, J, Gaasterland, D, Gaasterland, T, Haines, JL, Hark, L, Hauser, M, Kang, JH, Kraft, P, Lee, R, Lichter, P, Liu, Y, Moroi, S, Pericak, M, Realini, A, Rhee, D, Richards, JR, Ritch, R, Scott, WK, Singh, K, Sit, A, Vollrath, D, Weinreb, R, Wollstein, G, Wilmer, DZ, Gerhold-Ay, A, Nickels, S, Wilson, JF, Hayward, C, Boutin, TS, Polasek, O, Aung, T, Khor, CC, Amin, N, Lotery, AJ, Wiggs, JL, Cheng, C-Y, Hysi, PG, Hammond, CJ, Thiadens, AAHJ, MacGregor, S, Klaver, CCW, and van Duijn, CM

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019

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

Author

Tedja, MS, Wojciechowski, R, Hysi, PG, Eriksson, N, Furlotte, NA, Verhoeven, VJM, Iglesias, AI, Meester-Smoor, MA, Tompson, SW, Fan, Q, Khawaja, AP, Cheng, C-Y, 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, W-Y, Tai, E-S, Sim, XL, Huffman, JE, Polašek, O, Hayward, C, Bencic, G, Rudan, I, Wilson, JF, Consortium, Cream, Team, 23Andme Research, Consortium, Uk Biobank Eye And Vision, Joshi, PK, Tsujikawa, A, Matsuda, F, Whisenhunt, KN, Zeller, T, Van Der Spek, PJ, Haak, R, Meijers-Heijboer, H, Van Leeuwen, EM, Iyengar, SK, Lass, JH, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Vingerling, JR, Lehtimäki, T, Raitakari, OT, Biino, G, Concas, MP, Schwantes-An, T-H, Igo, RP, Cuellar-Partida, G, Martin, NG, Craig, JE, Gharahkhani, P, Williams, KM, Nag, A, Rahi, JS, Cumberland, PM, Delcourt, C, Bellenguez, C, Ried, JS, Bergen, AA, Meitinger, T, Gieger, C, Wong, TY, Hewitt, AW, Mackey, DA, Simpson, CL, Pfeiffer, N, Pärssinen, O, Baird, PN, Vitart, V, Amin, N, Van Duijn, CM, Bailey-Wilson, JE, Young, TL, Saw, S-M, Stambolian, D, Macgregor, S, Guggenheim, JA, Tung, JY, Hammond, CJ, Klaver, CCW, Netherlands Institute for Neuroscience (NIN), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, Tedja, Milly S [0000-0003-0356-9684], Hysi, Pirro G [0000-0001-5752-2510], Verhoeven, Virginie JM [0000-0001-7359-7862], Iglesias, Adriana I [0000-0001-5532-764X], Tompson, Stuart W [0000-0001-9788-6730], Khawaja, Anthony P [0000-0001-6802-8585], Yamashiro, Kenji [0000-0001-9354-8558], Wedenoja, Juho [0000-0002-6155-0378], Jonas, Jost B [0000-0003-2972-5227], Wang, Ya Xing [0000-0003-2749-7793], Foster, Paul J [0000-0002-4755-177X], Klein, Ronald [0000-0002-4428-6237], Shah, Rupal L [0000-0001-8789-8869], Hayward, Caroline [0000-0002-9405-9550], Rudan, Igor [0000-0001-6993-6884], Wilson, James F [0000-0001-5751-9178], Joshi, Peter K [0000-0002-6361-5059], Whisenhunt, Kristina N [0000-0003-2412-7666], Rivadeneira, Fernando [0000-0001-9435-9441], Biino, Ginevra [0000-0002-9936-946X], Gharahkhani, Puya [0000-0002-4203-5952], Williams, Katie M [0000-0003-4596-3938], Delcourt, Cécile [0000-0002-2099-0481], Bellenguez, Céline [0000-0002-1240-7874], Hewitt, Alex W [0000-0002-5123-5999], Baird, Paul N [0000-0002-1305-3502], Bailey-Wilson, Joan E [0000-0002-9153-2920], Young, Terri L [0000-0001-6994-9941], Guggenheim, Jeremy A [0000-0001-5164-340X], Hammond, Christopher J [0000-0002-3227-2620], Klaver, Caroline CW [0000-0002-2355-5258], Apollo - University of Cambridge Repository, Epidemiology, Ophthalmology, Clinical Genetics, Pathology, Internal Medicine, Graduate School, Human Genetics, Experimental Immunology, ANS - Complex Trait Genetics, and ARD - Amsterdam Reproduction and Development

Subjects
0301 basic medicine, Adult, Male, Cell type, ResearchInstitutes_Networks_Beacons/MICRA, In silico, taittovirheet, Genome-wide association study, Retinal Pigment Epithelium, Biology, Blindness, Polymorphism, Single Nucleotide, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, Retina, White People, 03 medical and health sciences, HIGH-GRADE MYOPIA, RETINAL-PIGMENT EPITHELIUM, SEROTONIN PATHWAY GENES, FORM-DEPRIVATION MYOPIA, COMMON VARIANTS, OCULAR GROWTH, RETINITIS-PIGMENTOSA, GENOTYPE IMPUTATION, MISSENSE MUTATIONS, DOPAMINE-RECEPTORS, Asian People, refractive errors, Retinitis pigmentosa, Genetics, medicine, Myopia, Journal Article, Humans, Genetic Predisposition to Disease, 610 Medicine & health, Regulation of gene expression, Retinal pigment epithelium, medicine.disease, Refractive Errors, 030104 developmental biology, medicine.anatomical_structure, Manchester Institute for Collaborative Research on Ageing, Gene Expression Regulation, genetic factors, Eye disorder, Female, sense organs, geneettiset tekijät, Neuroscience, Genome-Wide Association Study, Signal Transduction
Abstract

Skin affections after sulfur mustard (SM) exposure include erythema, blister formation and severe inflammation. An antidote or specific therapy does not exist. Anti-inflammatory compounds as well as substances counteracting SM-induced cell death are under investigation. In this study, we investigated the benzylisoquinoline alkaloide berberine (BER), a metabolite in plants like berberis vulgaris, which is used as herbal pharmaceutical in Asian countries, against SM toxicity using a well-established in vitro approach. Keratinocyte (HaCaT) mono-cultures (MoC) or HaCaT/THP-1 co-cultures (CoC) were challenged with 100, 200 or 300 mM SM for 1 h. Post-exposure, both MoC and CoC were treated with 10, 30 or 50 mu M BER for 24 h. At that time, supernatants were collected and analyzed both for interleukine (IL) 6 and 8 levels and for content of adenylate-kinase (AK) as surrogate marker for cell necrosis. Cells were lysed and nucleosome formation as marker for late apoptosis was assessed. In parallel, AK in cells was determined for normalization purposes. BER treatment did not influence necrosis, but significantly decreased apoptosis. Anti-inflammatory effects were moderate, but also significant, primarily in CoC. Overall, BER has protective effects against SM toxicity in vitro. Whether this holds true should be evaluated in future in vivo studies.

Published
2018

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

Author

Tedja, M.S., Wojciechowski, R., Hysi, P.G., Eriksson, N., Furlotte, N.A., Verhoeven, V.J., Iglesias, A.I., Meester-Smoor, M.A., Tompson, S.W., Fan, Q., Khawaja, A.P., Cheng, C.Y., Hohn, R., Yamashiro, K., Wenocur, A., Grazal, C., Haller, T., Metspalu, A., Wedenoja, J., Jonas, J.B., Wang, Y.X., Xie, J, Mitchell, P., Foster, P.J., Klein, B.E., Klein, R., Paterson, A.D., Hosseini, S.M., Shah, R.L., Williams, C., Teo, Y.Y., Tham, Y.C., Gupta, P., Zhao, W., Shi, Yuan, Saw, W.Y., Tai, E.S., Sim, X.L., Huffman, J.E., Polasek, O., Hayward, C., Bencic, G., Rudan, I., Wilson, J.F., Joshi, P.K., Tsujikawa, A., Matsuda, F., Whisenhunt, K.N., Zeller, T., Spek, P.J. van der, Haak, R., Meijers-Heijboer, H., Leeuwen, E.M. van, Iyengar, S.K., Lass, J.H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Vingerling, J.R., Lehtimaki, T., Raitakari, O.T., Biino, G., Concas, M.P., Schwantes-An, T.H., Igo, R.P., Jr., Cuellar-Partida, G., Martin, N.G., Craig, J.E., Gharahkhani, P., Williams, K.M., Nag, A., Rahi, J.S., Cumberland, P.M., Delcourt, C, Bellenguez, C., Ried, J.S., Bergen, A.A., Meitinger, T., Gieger, C., Wong, T.Y., Hewitt, A.W., Mackey, D.A., Simpson, C.L., Pfeiffer, N., Parssinen, O., Baird, P.N., Vitart, V., Amin, N., Duijn, C.M. van, Bailey-Wilson, J.E., Young, T.L., Saw, S.M., Stambolian, D., MacGregor, S., Guggenheim, J.A., Tung, J.Y., Hammond, C.J., Klaver, C.C.W., Tedja, M.S., Wojciechowski, R., Hysi, P.G., Eriksson, N., Furlotte, N.A., Verhoeven, V.J., Iglesias, A.I., Meester-Smoor, M.A., Tompson, S.W., Fan, Q., Khawaja, A.P., Cheng, C.Y., Hohn, R., Yamashiro, K., Wenocur, A., Grazal, C., Haller, T., Metspalu, A., Wedenoja, J., Jonas, J.B., Wang, Y.X., Xie, J, Mitchell, P., Foster, P.J., Klein, B.E., Klein, R., Paterson, A.D., Hosseini, S.M., Shah, R.L., Williams, C., Teo, Y.Y., Tham, Y.C., Gupta, P., Zhao, W., Shi, Yuan, Saw, W.Y., Tai, E.S., Sim, X.L., Huffman, J.E., Polasek, O., Hayward, C., Bencic, G., Rudan, I., Wilson, J.F., Joshi, P.K., Tsujikawa, A., Matsuda, F., Whisenhunt, K.N., Zeller, T., Spek, P.J. van der, Haak, R., Meijers-Heijboer, H., Leeuwen, E.M. van, Iyengar, S.K., Lass, J.H., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Vingerling, J.R., Lehtimaki, T., Raitakari, O.T., Biino, G., Concas, M.P., Schwantes-An, T.H., Igo, R.P., Jr., Cuellar-Partida, G., Martin, N.G., Craig, J.E., Gharahkhani, P., Williams, K.M., Nag, A., Rahi, J.S., Cumberland, P.M., Delcourt, C, Bellenguez, C., Ried, J.S., Bergen, A.A., Meitinger, T., Gieger, C., Wong, T.Y., Hewitt, A.W., Mackey, D.A., Simpson, C.L., Pfeiffer, N., Parssinen, O., Baird, P.N., Vitart, V., Amin, N., Duijn, C.M. van, Bailey-Wilson, J.E., Young, T.L., Saw, S.M., Stambolian, D., MacGregor, S., Guggenheim, J.A., Tung, J.Y., Hammond, C.J., and Klaver, C.C.W.

Abstract

Item does not contain fulltext, 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.

Published
2018

22. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma

Author

King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), Zeller, T. (Tanja), King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), and Zeller, T. (Tanja)

Abstract

Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60–100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10−6 for SNP rs7631

Published
2018
Full Text
View/download PDF

25. Fractional discrete model of an electrical drive with brushless micro-motor.

Author

MATUSIAK, M., BĄKAŁA, M., WOJCIECHOWSKI, R., and OSTALCZYK, P.

Subjects
FRACTIONAL calculus, CALCULUS, BRUSHLESS direct current electric motors, SYSTEM identification, INTEGERS, FRACTIONAL programming
Abstract

The use of fractional-order calculus for system modeling is a good alternative to well-known classic integer-order methods, primarily due to the precision with which the modeled object may be mapped. In this study, we created integer and fractional discrete models of a real object – a highspeed brushless micro-motor. The accuracy of the models was verified and compared. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

27. SAFETY AND EFFICACY OF SUBCUTANEOUS (S.C.) DOSE IANALUMAB (VAY736; ANTI-BAFFR mAb) ADMINISTERED MONTHLY OVER 28 WEEKS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE).

Author

Cortés-Hernández, J., Ignatenko, S., Gordienko, A., Agmon-Levin, N., Narongroeknawin, P., Romanowska-Prochnicka, K., Shen, N., Ciferská, H., Kodera, M., Wei, J. C. C., Leszczynski, P., Lan, J. L., Wojciechowski, R., Tarr, T., Vishneva, E., Chen, Y. H., Kaneko, Y., Finzel, S., Hoi, A., and Okada, M.

Published
2023
Full Text
View/download PDF

28. Genetically low vitamin D concentrations and myopic refractive error: A Mendelian randomization study

Author

Cuellar-Partida, G. (Gabriel), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Guggenheim, J. (Jean), Hewitt, A.W. (Alex W.), Williams, C. (Cathy), JinWang, J. (Jie), Kho, P.-F. (Pik-Fang), Saw, S-M. (Seang-Mei), Cheng, C-Y. (Ching-Yu), YinWong, T. (Tien), Aung, T. (Tin), LYoung, T. (Terri), Tideman, J.W.L. (Willem), Jonas, J.B. (Jost B.), Mitchell, P. (Paul), Wojciechowski, R. (Robert), Stambolian, D.E. (Dwight), Hysi, P.G. (Pirro), Hammond, C.J. (Christopher), Mackey, D.A. (David), Lucas, R.M. (Robyn M.), MacGregor, S. (Stuart), Cuellar-Partida, G. (Gabriel), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Guggenheim, J. (Jean), Hewitt, A.W. (Alex W.), Williams, C. (Cathy), JinWang, J. (Jie), Kho, P.-F. (Pik-Fang), Saw, S-M. (Seang-Mei), Cheng, C-Y. (Ching-Yu), YinWong, T. (Tien), Aung, T. (Tin), LYoung, T. (Terri), Tideman, J.W.L. (Willem), Jonas, J.B. (Jost B.), Mitchell, P. (Paul), Wojciechowski, R. (Robert), Stambolian, D.E. (Dwight), Hysi, P.G. (Pirro), Hammond, C.J. (Christopher), Mackey, D.A. (David), Lucas, R.M. (Robyn M.), and MacGregor, S. (Stuart)

Abstract

Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia. Methods: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in

Published
2017
Full Text
View/download PDF

29. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Author

Springelkamp, H. (Henriët), Iglesias, A.I. (Adriana), Mishra, A. (Aniket), Höhn, R. (René), Wojciechowski, R. (Robert), Khawaja, A.P. (Anthony), Nag, A. (Abhishek), Wang, Y.X. (Ya Xing), Wang, J.J. (Jie Jin), Cuellar-Partida, G. (Gabriel), Gibson, J. (Jane), Cooke Bailey, J.N. (Jessica), Vithana, E.N. (Eranga), Gharahkhani, P. (Puya), Boutin, T. (Thibaud), Ramdas, W.D. (Wishal), Zeller, T. (Tanja), Luben, R.N. (Robert), Yonova-Doing, E. (Ekaterina), Viswanathan, A.C. (Ananth), Yazar, S. (Seyhan), Cree, A.J. (Angela), Haines, J.L. (Jonathan), Koh, J.Y. (Jia Yu), Souzeau, E. (Emmanuelle), Wilson, J.F. (James), Amin, N. (Najaf), Müller, C. (Christian), Venturini, C. (Cristina), Kearns, L.S. (Lisa), Hee Kang, J. (Jae), Consortium, N. (Neighborhood), Tham, Y.C. (Yih Chung), Zhou, T. (Tiger), van Leeuwen, E.M. (Elisabeth), Nickels, S. (Stefan), Sanfilippo, P. (Paul), Liao, J. (Jiemin), Linde, H.V. (Herma van der), Zhao, W. (Wanting), van Koolwijk, L.M. (Leonieke), Zheng, L. (Li), Rivadeneira, F. (Fernando), Baskaran, M. (Mani), van der Lee, S.J. (Sven), Perera, S. (Shamira), de Jong, P.T. (Paulus), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Fan, Q. (Qiao), Hofman, A. (Albert), Shyong Tai, E. (E-), Vingerling, J.R. (Johannes), Sim, X. (Xueling), Wolfs, R.C. (Roger), Teo, Y.Y. (Yik Ying), Lemij, H.G. (Hans), Khor, C.C. (Chiea Chuen), Willemsen, R. (Rob), Lackner, K.J. (Karl), Aung, T. (Tin), Jansonius, N.M. (Nomdo), Montgomery, G. (Grant), Wild, P.S. (Philipp), Young, T.L. (Terri), Burdon, K.P. (Kathryn), Hysi, P.G. (Pirro), Pasquale, L.R. (Louis), Wong, T.Y. (Tien Yin), Klaver, C.C. (Caroline), Hewitt, A.W. (Alex), Jonas, J.B. (Jost), Mitchell, P. (Paul), Lotery, A.J. (Andrew), Foster, P.J. (Paul), Vitart, V. (Veronique), Pfeiffer, N. (Norbert), Craig, J.E. (Jamie), Mackey, D.A. (David), Hammond, C.J. (Christopher), Wiggs, J.L. (Janey), Cheng, C.Y. (Ching-Yu), van Duijn, C.M. (Cornelia), MacGregor, S. (Stuart), Springelkamp, H. (Henriët), Iglesias, A.I. (Adriana), Mishra, A. (Aniket), Höhn, R. (René), Wojciechowski, R. (Robert), Khawaja, A.P. (Anthony), Nag, A. (Abhishek), Wang, Y.X. (Ya Xing), Wang, J.J. (Jie Jin), Cuellar-Partida, G. (Gabriel), Gibson, J. (Jane), Cooke Bailey, J.N. (Jessica), Vithana, E.N. (Eranga), Gharahkhani, P. (Puya), Boutin, T. (Thibaud), Ramdas, W.D. (Wishal), Zeller, T. (Tanja), Luben, R.N. (Robert), Yonova-Doing, E. (Ekaterina), Viswanathan, A.C. (Ananth), Yazar, S. (Seyhan), Cree, A.J. (Angela), Haines, J.L. (Jonathan), Koh, J.Y. (Jia Yu), Souzeau, E. (Emmanuelle), Wilson, J.F. (James), Amin, N. (Najaf), Müller, C. (Christian), Venturini, C. (Cristina), Kearns, L.S. (Lisa), Hee Kang, J. (Jae), Consortium, N. (Neighborhood), Tham, Y.C. (Yih Chung), Zhou, T. (Tiger), van Leeuwen, E.M. (Elisabeth), Nickels, S. (Stefan), Sanfilippo, P. (Paul), Liao, J. (Jiemin), Linde, H.V. (Herma van der), Zhao, W. (Wanting), van Koolwijk, L.M. (Leonieke), Zheng, L. (Li), Rivadeneira, F. (Fernando), Baskaran, M. (Mani), van der Lee, S.J. (Sven), Perera, S. (Shamira), de Jong, P.T. (Paulus), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Fan, Q. (Qiao), Hofman, A. (Albert), Shyong Tai, E. (E-), Vingerling, J.R. (Johannes), Sim, X. (Xueling), Wolfs, R.C. (Roger), Teo, Y.Y. (Yik Ying), Lemij, H.G. (Hans), Khor, C.C. (Chiea Chuen), Willemsen, R. (Rob), Lackner, K.J. (Karl), Aung, T. (Tin), Jansonius, N.M. (Nomdo), Montgomery, G. (Grant), Wild, P.S. (Philipp), Young, T.L. (Terri), Burdon, K.P. (Kathryn), Hysi, P.G. (Pirro), Pasquale, L.R. (Louis), Wong, T.Y. (Tien Yin), Klaver, C.C. (Caroline), Hewitt, A.W. (Alex), Jonas, J.B. (Jost), Mitchell, P. (Paul), Lotery, A.J. (Andrew), Foster, P.J. (Paul), Vitart, V. (Veronique), Pfeiffer, N. (Norbert), Craig, J.E. (Jamie), Mackey, D.A. (David), Hammond, C.J. (Christopher), Wiggs, J.L. (Janey), Cheng, C.Y. (Ching-Yu), van Duijn, C.M. (Cornelia), and MacGregor, S. (Stuart)

Abstract

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

Published
2017
Full Text
View/download PDF

30. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Author

Springelkamp, H., Iglesias, A.I., Mishra, A, Hohn, R., Wojciechowski, R., Khawaja, A.P., Nag, A., Wang, Y.X., Wang, J.J., Cuellar-Partida, G., Gibson, J., Bailey, J.N., Vithana, E.N., Gharahkhani, P., Boutin, T., Ramdas, W.D., Zeller, T., Luben, R.N., Yonova-Doing, E., Viswanathan, A.C., Yazar, S., Cree, A.J., Haines, J.L., Koh, J.Y., Souzeau, E., Wilson, J.F., Amin, N., Muller, C., Venturini, C., Kearns, L.S., Kang, J.H., Tham, Y.C., Zhou, T., Leeuwen, E.M. van, Nickels, S., Sanfilippo, P., Liao, J., Linde, H. van der, Zhao, W., Koolwijk, L.M. van, Zheng, L., Rivadeneira, F., Baskaran, M., Lee, S.J. van der, Perera, S., Jong, P.T., Oostra, B.A., Uitterlinden, A.G., Fan, Q., Hofman, A., Tai, E.S., Vingerling, J.R., Sim, X., Wolfs, R.C., Teo, Y.Y., Lemij, H.G., Khor, C.C., Willemsen, R., Lackner, K.J., Aung, T., Jansonius, N.M., Montgomery, G., Wild, P.S., Young, T.L., Burdon, K.P., Hysi, P.G., Pasquale, L.R., Wong, T.Y., Klaver, C.C.W., Hewitt, A.W., Jonas, J.B., Mitchell, P., Lotery, A.J., Foster, P.J., Vitart, V., Pfeiffer, N., Craig, J.E., Mackey, D.A., Hammond, C.J., Wiggs, J.L., Cheng, C.Y., Duijn, C.M. van, MacGregor, S., Springelkamp, H., Iglesias, A.I., Mishra, A, Hohn, R., Wojciechowski, R., Khawaja, A.P., Nag, A., Wang, Y.X., Wang, J.J., Cuellar-Partida, G., Gibson, J., Bailey, J.N., Vithana, E.N., Gharahkhani, P., Boutin, T., Ramdas, W.D., Zeller, T., Luben, R.N., Yonova-Doing, E., Viswanathan, A.C., Yazar, S., Cree, A.J., Haines, J.L., Koh, J.Y., Souzeau, E., Wilson, J.F., Amin, N., Muller, C., Venturini, C., Kearns, L.S., Kang, J.H., Tham, Y.C., Zhou, T., Leeuwen, E.M. van, Nickels, S., Sanfilippo, P., Liao, J., Linde, H. van der, Zhao, W., Koolwijk, L.M. van, Zheng, L., Rivadeneira, F., Baskaran, M., Lee, S.J. van der, Perera, S., Jong, P.T., Oostra, B.A., Uitterlinden, A.G., Fan, Q., Hofman, A., Tai, E.S., Vingerling, J.R., Sim, X., Wolfs, R.C., Teo, Y.Y., Lemij, H.G., Khor, C.C., Willemsen, R., Lackner, K.J., Aung, T., Jansonius, N.M., Montgomery, G., Wild, P.S., Young, T.L., Burdon, K.P., Hysi, P.G., Pasquale, L.R., Wong, T.Y., Klaver, C.C.W., Hewitt, A.W., Jonas, J.B., Mitchell, P., Lotery, A.J., Foster, P.J., Vitart, V., Pfeiffer, N., Craig, J.E., Mackey, D.A., Hammond, C.J., Wiggs, J.L., Cheng, C.Y., Duijn, C.M. van, and MacGregor, S.

Abstract

Item does not contain fulltext, Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

Published
2017

31. Genetically low vitamin D concentrations and myopic refractive error: a Mendelian randomization study

Author

Cuellar-Partida, G, Williams, KM, Yazar, S, Guggenheim, JA, Hewitt, AW, Williams, C, Wang, JJ, Kho, P-F, Saw, SM, Cheng, C-Y, Wong, TY, Aung, T, Young, TL, Tideman, JWL, Jonas, JB, Mitchell, P, Wojciechowski, R, Stambolian, D, Hysi, P, Hammond, CJ, Mackey, DA, Lucas, RM, MacGregor, S, Cuellar-Partida, G, Williams, KM, Yazar, S, Guggenheim, JA, Hewitt, AW, Williams, C, Wang, JJ, Kho, P-F, Saw, SM, Cheng, C-Y, Wong, TY, Aung, T, Young, TL, Tideman, JWL, Jonas, JB, Mitchell, P, Wojciechowski, R, Stambolian, D, Hysi, P, Hammond, CJ, Mackey, DA, Lucas, RM, and MacGregor, S

Abstract

BACKGROUND: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia. METHODS: We performed MR using results from a meta-analysis of refractive error (RE) genome-wide association study (GWAS) that included 37 382 and 8 376 adult participants of European and Asian ancestry, respectively, published by the Consortium for Refractive Error And Myopia (CREAM). We used single nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH)D concentration as instrumental variables (IV). We estimated the effect of 25(OH)D on myopia level using a Wald-type ratio estimator based on the effect estimates from the CREAM GWAS. RESULTS: Using the combined effect attributed to the four SNPs, the estimate for the effect of 25(OH)D on refractive error was -0.02 [95% confidence interval (CI) -0.09, 0.04] dioptres (D) per 10 nmol/l increase in 25(OH)D concentration in Caucasians and 0.01 (95% CI -0.17, 0.19) D per 10 nmol/l increase in Asians. CONCLUSIONS: The tight confidence intervals on our estimates suggest the true contribution of vitamin D levels to degree of myopia is very small and indistinguishable from zero. Previous findings from observational studies linking vitamin D levels to myopia were likely attributable to the effects of confounding by time spent outdoors.

Published
2017

32. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Author

Springelkamp, Henriët, Iglesias Gonzalez, Adriana, Mishra, A, Hohn, R, Wojciechowski, R, Khawaja, AP, Nag, A, Wang, YX, Wang, JJ, Cuellar-Partida, G, Gibson, J, Bailey, JNC, Vithana, EN, Gharahkhani, P, Boutin, T, Ramdas, Wishal, Zeller, T, Luben, RN, Yonova-Doing, E, Viswanathan, AC, Yazar, S, Cree, AJ, Haines, JL, Koh, JY, Souzeau, E, Wilson, JF, Amin, Najaf, Muller, C, Venturini, C, Kearns, LS, Kang, JH, Tham, YC, Zhou, T, van Leeuwen, EM, Nickels, S, Sanfilippo, P, Liao, JM, van der Linde, HC, Zhao, WT, Koolwijk, Leonieke, Zheng, L, Rivadeneira, Fernando, Baskaran, M, van der Lee, Sven, Perera, S, Jong, P, Oostra, Ben, Uitterlinden, André, Fan, Q, Hofman, Bert, Tai, ES, Vingerling, Hans, Sim, XL, Wolfs, R.C.W., Teo, YY, Lemij, HG, Khor, CC, Willemsen, Rob, Lackner, KJ, Aung, T, Jansonius, NM, Montgomery, G, Wild, PS, Young, TL, Burdon, KP, Hysi, PG, Pasquale, LR, Wong, TY, Klaver, Caroline, Hewitt, AW, Jonas, JB, Mitchell, P, Lotery, AJ, Foster, PJ, Vitart, V, Pfeiffer, N, Craig, JE, Mackey, DA, Hammond, CJ, Wiggs, JL, Cheng, CY (Ching-Yu), Duijn, Cornelia, Macgregor, S, Springelkamp, Henriët, Iglesias Gonzalez, Adriana, Mishra, A, Hohn, R, Wojciechowski, R, Khawaja, AP, Nag, A, Wang, YX, Wang, JJ, Cuellar-Partida, G, Gibson, J, Bailey, JNC, Vithana, EN, Gharahkhani, P, Boutin, T, Ramdas, Wishal, Zeller, T, Luben, RN, Yonova-Doing, E, Viswanathan, AC, Yazar, S, Cree, AJ, Haines, JL, Koh, JY, Souzeau, E, Wilson, JF, Amin, Najaf, Muller, C, Venturini, C, Kearns, LS, Kang, JH, Tham, YC, Zhou, T, van Leeuwen, EM, Nickels, S, Sanfilippo, P, Liao, JM, van der Linde, HC, Zhao, WT, Koolwijk, Leonieke, Zheng, L, Rivadeneira, Fernando, Baskaran, M, van der Lee, Sven, Perera, S, Jong, P, Oostra, Ben, Uitterlinden, André, Fan, Q, Hofman, Bert, Tai, ES, Vingerling, Hans, Sim, XL, Wolfs, R.C.W., Teo, YY, Lemij, HG, Khor, CC, Willemsen, Rob, Lackner, KJ, Aung, T, Jansonius, NM, Montgomery, G, Wild, PS, Young, TL, Burdon, KP, Hysi, PG, Pasquale, LR, Wong, TY, Klaver, Caroline, Hewitt, AW, Jonas, JB, Mitchell, P, Lotery, AJ, Foster, PJ, Vitart, V, Pfeiffer, N, Craig, JE, Mackey, DA, Hammond, CJ, Wiggs, JL, Cheng, CY (Ching-Yu), Duijn, Cornelia, and Macgregor, S

Published
2017

34. Assessing the genetic predisposition of education on myopia: A mendelian randomization study

Author

Cuellar-Partida, G., Lu, Y., Kho, P.F., Hewitt, A.W., Wichmann, H.-E., Yazar, S., Stambolian, D., Bailey-Wilson, J.E., Wojciechowski, R., Wang, J.J., Mitchell, P., Mackey, D.A., and MacGregor, S.

Subjects
Education, Instrumental Variable, Mendelian Randomization, Myopia, Polygenic Risk Scores, Refractive Error, genetic structures
Abstract

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10-3). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [∼2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error.

Published
2016

35. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author

Fan, Q., Guo, X., Tideman, J.W.L., Williams, K.M., Yazar, S., Hosseini, S.M., Howe, L.D., Pourcain, B.S., Evans, D.M., Timpson, N.J., McMahon, G., Hysi, P.G., Krapohl, E., Wang, Y.X., Jonas, J.B., Baird, P.N., Wang, J.J., Cheng, C.Y., Teo, Y.Y., Wong, T.Y., Ding, X., Wojciechowski, R., Young, T.L., Pärssinen, O., Oexle, K., Pfeiffer, N., Bailey-Wilson, J.E., Paterson, A.D., Klaver, C.C.W., Plomin, R., Hammond, C.J., He, M., Saw, S.M., Guggenheim, J.A., Meguro, A., Wright, A.F., Hewitt, A.W., Young, A.L., Veluchamy, A.B., Metspalu, A., The CREAM Consortium (Döring, A., Gieger, C., Ried, J.S.), Khawaja, A.P., Klein, B.E., St Pourcain, B., Fleck, B., Hayward, C., Williams, C., Delcourt, C., Pang, C.P., Khor, C.C., Simpson, C.L., van Duijn, C.M., Mackey, D.A., Stambolian, D., Chew, E., Tai, E.S., Mihailov, E., Smith, G.D., Biino, G., Campbell, H., Rudan, I., Seppälä, I., Kaprio, J., Wilson, J.F., and Craig, J.E.

Abstract

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Published
2016

36. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author

Fan, Q, Guo, X, Tideman, Willem, Williams, KM, Yazar, S, Hosseini, SM, Howe, LD, St Pourcain, B, Evans, DM, Timpson, NJ, McMahon, G, Hysi, PG, Krapohl, E, Wang, YX, Jonas, JB, Baird, PN, Wang, JJ, Cheng, CY (Ching-Yu), Teo, YY, Wong, TY, Ding, X, Wojciechowski, R, Young, TL, Parssinen, O, Oexle, K, Pfeiffer, N, Bailey-Wilson, JE, Paterson, AD, Klaver, Caroline, Plomin, R, Hammond, CJ, Mackey, DA, He, MG, Saw, SM, Williams, C, Guggenheim, JA, Epidemiology, and Ophthalmology

Subjects
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
Abstract

Contains fulltext : 167190.pdf (Publisher’s version ) (Open Access) Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Published
2016

37. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author

Fan, Q., Verhoeven, V.J., Wojciechowski, R., Barathi, V.A., Hysi, P.G., Guggenheim, J.A., Hohn, R., Vitart, V., Khawaja, A.P., Yamashiro, K., Hosseini, S.M., Lehtimaki, T., Lu, Y., Haller, T., Xie, J., Delcourt, C, Pirastu, M., Wedenoja, J., Gharahkhani, P., Venturini, C., Miyake, M., Hewitt, A.W., Guo, X., Mazur, J., Huffman, J.E., Williams, K.M., Polasek, O., Campbell, H., Rudan, I., Vatavuk, Z., Wilson, J.F., Joshi, P.K., McMahon, G., St Pourcain, B., Evans, D.M., Simpson, C.L., Schwantes-An, T.H., Igo, R.P., Jr., Mirshahi, A., Cougnard-Gregoire, A., Bellenguez, C., Blettner, M., Raitakari, O., Kahonen, M., Seppala, I., Zeller, T., Meitinger, T., Ried, J.S., Gieger, C., Portas, L., Leeuwen, E.M. van, Amin, N., Uitterlinden, A.G., Rivadeneira, F., Hofman, A., Vingerling, J.R., Wang, Y.X., Wang, X., Boh, E.T.H., Ikram, M.K., Sabanayagam, C., Gupta, P., Tan, V., Zhou, L, Ho, C.E., Lim, W., Beuerman, R.W., Siantar, R., Tai, E.S., Vithana, E., Mihailov, E., Khor, C.C., Hayward, C., Luben, R.N., Foster, P.J., Klein, B.E., Klein, R., Wong, H.S., Mitchell, P., Metspalu, A., Aung, T., Young, T.L., He, M., Parssinen, O., Duijn, C.M. van, Wang, J.J., Williams, C., Jonas, J.B., Teo, Y.Y., Mackey, D.A., Oexle, K., Yoshimura, N., Paterson, A.D., Pfeiffer, N., Wong, T.Y., Baird, P.N., Stambolian, D., Wilson, J.E., Cheng, C.Y., Hammond, C.J., Klaver, C.C.W., et al., Fan, Q., Verhoeven, V.J., Wojciechowski, R., Barathi, V.A., Hysi, P.G., Guggenheim, J.A., Hohn, R., Vitart, V., Khawaja, A.P., Yamashiro, K., Hosseini, S.M., Lehtimaki, T., Lu, Y., Haller, T., Xie, J., Delcourt, C, Pirastu, M., Wedenoja, J., Gharahkhani, P., Venturini, C., Miyake, M., Hewitt, A.W., Guo, X., Mazur, J., Huffman, J.E., Williams, K.M., Polasek, O., Campbell, H., Rudan, I., Vatavuk, Z., Wilson, J.F., Joshi, P.K., McMahon, G., St Pourcain, B., Evans, D.M., Simpson, C.L., Schwantes-An, T.H., Igo, R.P., Jr., Mirshahi, A., Cougnard-Gregoire, A., Bellenguez, C., Blettner, M., Raitakari, O., Kahonen, M., Seppala, I., Zeller, T., Meitinger, T., Ried, J.S., Gieger, C., Portas, L., Leeuwen, E.M. van, Amin, N., Uitterlinden, A.G., Rivadeneira, F., Hofman, A., Vingerling, J.R., Wang, Y.X., Wang, X., Boh, E.T.H., Ikram, M.K., Sabanayagam, C., Gupta, P., Tan, V., Zhou, L, Ho, C.E., Lim, W., Beuerman, R.W., Siantar, R., Tai, E.S., Vithana, E., Mihailov, E., Khor, C.C., Hayward, C., Luben, R.N., Foster, P.J., Klein, B.E., Klein, R., Wong, H.S., Mitchell, P., Metspalu, A., Aung, T., Young, T.L., He, M., Parssinen, O., Duijn, C.M. van, Wang, J.J., Williams, C., Jonas, J.B., Teo, Y.Y., Mackey, D.A., Oexle, K., Yoshimura, N., Paterson, A.D., Pfeiffer, N., Wong, T.Y., Baird, P.N., Stambolian, D., Wilson, J.E., Cheng, C.Y., Hammond, C.J., Klaver, C.C.W., and et al.

Abstract

Contains fulltext : 167942.pdf (publisher's version ) (Open Access), Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP x education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 x 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Published
2016

38. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author

Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)

Abstract

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Published
2016
Full Text
View/download PDF

39. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author

Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)

Abstract

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Published
2016
Full Text
View/download PDF

40. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author

Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, Makela, KM, Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, and Makela, KM

Abstract

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Published
2016

41. A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort

Author

Nag, A., Venturini, C., Small, K.S., Young, T. L., Viswanathan, A.C., Mackey, D.A., Hysi, P.G., Hammond, C., Aung, T., Cheng, C.-Y., Fleck, B.W., Gibson, J., Hewitt, A.W., Hofman, A., Hohn, R., Jonas, J.B., Khor, C.-C., Klaver, C.C., Lemij, H.G., Liao, J., Lotery, A.J., Lu, Y., Macgregor, S., Mitchell, P., Ramdas, W.D., Springelkamp, H., Tai, E.-S., Teo, Y.-Y., Uitterlinden, A.G., van Duijn, C.M., van Koolwijk, L.M., Vingerling, J.R., Vitart, V., Vithana, E., Wang, J.J., Williams, K.M., Wojciechowski, R., Wong, T.-Y., WTCCC, None, Xu, L., Yonova-Doing, E., and Tanja, Z.

Subjects
genetic structures, eye diseases
Abstract

Glaucoma is a major cause of blindness in the world. To date, common genetic variants associated with glaucoma only explain a small proportion of its heritability. We performed a genome-wide association study of intra-ocular pressure (IOP), an underlying endophenotype for glaucoma. The discovery phase of the study was carried out in the TwinsUK cohort (N = 2774) analyzing association between IOP and single nucleotide polymorphisms (SNPs) imputed to HapMap2. The results were validated in 12 independent replication cohorts of European ancestry (combined N = 22 789) that were a part of the International Glaucoma Genetics Consortium. Expression quantitative trait locus (eQTL) analyses of the significantly associated SNPs were performed using data from the Multiple Tissue Human Expression Resource (MuTHER) Study. In the TwinsUK cohort, IOP was significantly associated with a number of SNPs at 9q33.3 (P = 3.48 × 10(-8) for rs2286885, the most significantly associated SNP at this locus), within the genomic sequence of the FAM125B gene. Independent replication in a composite panel of 12 cohorts revealed consistent direction of effect and significant association (P = 0.003, for fixed-effect meta-analysis). Suggestive evidence for an eQTL effect of rs2286885 was observed for one of the probes targeting the coding region of the FAM125B gene. This gene codes for a component of a membrane complex involved in vesicular trafficking process, a function similar to that of the Caveolin genes (CAV1 and CAV2) which have previously been associated with primary open-angle glaucoma. This study suggests a novel association between SNPs in FAM125B and IOP in the TwinsUK cohort, though further studies to elucidate the functional role of this gene in glaucoma are necessary.

Published
2014

42. APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans

Author

Tkatchenko, A.V. (Andrei V.), Tkatchenko, T.V. (Tatiana V.), Guggenheim, J. (Jean), Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Wojciechowski, R. (Robert), Singh, P.K. (Pawan Kumar), Kumar, A. (Ashok), Thinakaran, G. (Gopal), Williams, C. (Cathy), Tkatchenko, A.V. (Andrei V.), Tkatchenko, T.V. (Tatiana V.), Guggenheim, J. (Jean), Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Wojciechowski, R. (Robert), Singh, P.K. (Pawan Kumar), Kumar, A. (Ashok), Thinakaran, G. (Gopal), and Williams, C. (Cathy)

Abstract

Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (“missing heritability”). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5’-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10−4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10−3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10−3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p < 1.0 × 10−4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10−4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10−4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p < 1.0 × 10−4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10−4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the “missing” myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high leve

Published
2015
Full Text
View/download PDF

43. Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

Author

Li, Q. (Qing), Wojciechowski, R. (Robert), Simpson, C.L. (Claire), Hysi, P.G. (Pirro), Verhoeven, V.J.M. (Virginie), Ikram, M.K. (Kamran), Höhn, R. (René), Vitart, V. (Veronique), Hewit, A.W. (Alex), Oexle, K. (Konrad), Makela, K.M. (Kari Matti), MacGregor, S. (Stuart), Pirastu, M. (Mario), Fan, Q. (Qiao), Cheng, C-Y. (Ching-Yu), St Pourcain, B. (Beate), Mcmahon, G. (George), Kemp, J.P. (John), Northstone, K. (Kate), Rahi, J.S. (Jugnoo), Cumberland, P. (Phillippa), Martin, N.G. (Nicholas), Sanfilippo, P.G. (Paul G.), Lu, Y. (Yi), Wang, Y. (Ying), Hayward, C. (Caroline), Polasek, O. (Ozren), Campbell, H. (Harry), Bencic, G. (Goran), Wright, A. (Alan), Wedenoja, J. (Juho), Zeller, T. (Tanja), Schillert, A. (Arne), Mirshahi, A. (Alireza), Lackner, K.J. (Karl), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K. H.), Ried, J.S. (Janina), Gieger, C. (Christian), Murgia, D. (Daniela), Wilson, J.F. (James F), Fleck, B.W. (Brian W.), Yazar, S. (Seyhan), Vingerling, J.R. (Hans), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Amin, N. (Najaf), Karssen, L.C. (Lennart), Oostra, B.A. (Ben), Zhou, X. (Xin), Teo, Y.Y. (Yik Ying), Tai, E.S. (Shyong), Vithana, E.N. (Eranga), Barathi, V.A. (Veluchamy), Zheng, Y. (Yingfeng), Siantar, R. (Rosalynn), Neelam, K. (Kumari), Shin, Y. (Youchan), Lam, J. (Janice), Yonova-Doing, E. (Ekaterina), Venturini, C. (Cristina), Hosseini, S.M. (S Mohsen), Wong, H.-S. (Hoi-Suen), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Raitakari, O. (Olli), Timpson, N.J. (Nicholas), Evans, D.M. (David M.), Khor, C.C., Aung, T. (Tin), Young, T.L. (Terri), Mitchell, P. (Paul), Klein, B.E.K. (Barbara), Duijn, C.M. (Cornelia) van, Meitinger, T. (Thomas), Jonas, J.B. (Jost B.), Baird, P.N. (Paul), Mackey, D.A. (David), Wong, T.Y. (Tien Yin), Saw, S-M. (Seang-Mei), Pärssinen, O. (Olavi), Stambolian, D.E. (Dwight), Hammond, C.J. (Christopher), Klaver, C.C.W. (Caroline), Williams, C. (Cathy), Paterson, A.D. (Andrew), Bailey-Wilson, J.E. (Joan E.), Guggenheim, J. (Jean), Li, Q. (Qing), Wojciechowski, R. (Robert), Simpson, C.L. (Claire), Hysi, P.G. (Pirro), Verhoeven, V.J.M. (Virginie), Ikram, M.K. (Kamran), Höhn, R. (René), Vitart, V. (Veronique), Hewit, A.W. (Alex), Oexle, K. (Konrad), Makela, K.M. (Kari Matti), MacGregor, S. (Stuart), Pirastu, M. (Mario), Fan, Q. (Qiao), Cheng, C-Y. (Ching-Yu), St Pourcain, B. (Beate), Mcmahon, G. (George), Kemp, J.P. (John), Northstone, K. (Kate), Rahi, J.S. (Jugnoo), Cumberland, P. (Phillippa), Martin, N.G. (Nicholas), Sanfilippo, P.G. (Paul G.), Lu, Y. (Yi), Wang, Y. (Ying), Hayward, C. (Caroline), Polasek, O. (Ozren), Campbell, H. (Harry), Bencic, G. (Goran), Wright, A. (Alan), Wedenoja, J. (Juho), Zeller, T. (Tanja), Schillert, A. (Arne), Mirshahi, A. (Alireza), Lackner, K.J. (Karl), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K. H.), Ried, J.S. (Janina), Gieger, C. (Christian), Murgia, D. (Daniela), Wilson, J.F. (James F), Fleck, B.W. (Brian W.), Yazar, S. (Seyhan), Vingerling, J.R. (Hans), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Amin, N. (Najaf), Karssen, L.C. (Lennart), Oostra, B.A. (Ben), Zhou, X. (Xin), Teo, Y.Y. (Yik Ying), Tai, E.S. (Shyong), Vithana, E.N. (Eranga), Barathi, V.A. (Veluchamy), Zheng, Y. (Yingfeng), Siantar, R. (Rosalynn), Neelam, K. (Kumari), Shin, Y. (Youchan), Lam, J. (Janice), Yonova-Doing, E. (Ekaterina), Venturini, C. (Cristina), Hosseini, S.M. (S Mohsen), Wong, H.-S. (Hoi-Suen), Lehtimäki, T. (Terho), Kähönen, M. (Mika), Raitakari, O. (Olli), Timpson, N.J. (Nicholas), Evans, D.M. (David M.), Khor, C.C., Aung, T. (Tin), Young, T.L. (Terri), Mitchell, P. (Paul), Klein, B.E.K. (Barbara), Duijn, C.M. (Cornelia) van, Meitinger, T. (Thomas), Jonas, J.B. (Jost B.), Baird, P.N. (Paul), Mackey, D.A. (David), Wong, T.Y. (Tien Yin), Saw, S-M. (Seang-Mei), Pärssinen, O. (Olavi), Stambolian, D.E. (Dwight), Hammond, C.J. (Christopher), Klaver, C.C.W. (Caroline), Williams, C. (Cathy), Paterson, A.D. (Andrew), Bailey-Wilson, J.E. (Joan E.), and Guggenheim, J. (Jean)

Abstract

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical

Published
2015
Full Text
View/download PDF

44. Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

Author

Li, Q, Wojciechowski, R, Simpson, CL, Hysi, PG, Verhoeven, VJM, Ikram, MK, Hoehn, R, Vitart, V, Hewitt, AW, Oexle, K, Makela, K-M, MacGregor, S, Pirastu, M, Fan, Q, Cheng, C-Y, St Pourcain, B, McMahon, G, Kemp, JP, Northstone, K, Rahi, JS, Cumberland, PM, Martin, NG, Sanfilippo, PG, Lu, Y, Wang, YX, Hayward, C, Polasek, O, Campbell, H, Bencic, G, Wright, AF, Wedenoja, J, Zeller, T, Schillert, A, Mirshahi, A, Lackner, K, Yip, SP, Yap, MKH, Ried, JS, Gieger, C, Murgia, F, Wilson, JF, Fleck, B, Yazar, S, Vingerling, JR, Hofman, A, Uitterlinden, A, Rivadeneira, F, Amin, N, Karssen, L, Oostra, BA, Zhou, X, Teo, Y-Y, Tai, ES, Vithana, E, Barathi, V, Zheng, Y, Siantar, RG, Neelam, K, Shin, Y, Lam, J, Yonova-Doing, E, Venturini, C, Hosseini, SM, Wong, H-S, Lehtimaki, T, Kahonen, M, Raitakari, O, Timpson, NJ, Evans, DM, Khor, C-C, Aung, T, Young, TL, Mitchell, P, Klein, B, van Duijn, CM, Meitinger, T, Jonas, JB, Baird, PN, Mackey, DA, Wong, TY, Saw, S-M, Parssinen, O, Stambolian, D, Hammond, CJ, Klaver, CCW, Williams, C, Paterson, AD, Bailey-Wilson, JE, Guggenheim, JA, Li, Q, Wojciechowski, R, Simpson, CL, Hysi, PG, Verhoeven, VJM, Ikram, MK, Hoehn, R, Vitart, V, Hewitt, AW, Oexle, K, Makela, K-M, MacGregor, S, Pirastu, M, Fan, Q, Cheng, C-Y, St Pourcain, B, McMahon, G, Kemp, JP, Northstone, K, Rahi, JS, Cumberland, PM, Martin, NG, Sanfilippo, PG, Lu, Y, Wang, YX, Hayward, C, Polasek, O, Campbell, H, Bencic, G, Wright, AF, Wedenoja, J, Zeller, T, Schillert, A, Mirshahi, A, Lackner, K, Yip, SP, Yap, MKH, Ried, JS, Gieger, C, Murgia, F, Wilson, JF, Fleck, B, Yazar, S, Vingerling, JR, Hofman, A, Uitterlinden, A, Rivadeneira, F, Amin, N, Karssen, L, Oostra, BA, Zhou, X, Teo, Y-Y, Tai, ES, Vithana, E, Barathi, V, Zheng, Y, Siantar, RG, Neelam, K, Shin, Y, Lam, J, Yonova-Doing, E, Venturini, C, Hosseini, SM, Wong, H-S, Lehtimaki, T, Kahonen, M, Raitakari, O, Timpson, NJ, Evans, DM, Khor, C-C, Aung, T, Young, TL, Mitchell, P, Klein, B, van Duijn, CM, Meitinger, T, Jonas, JB, Baird, PN, Mackey, DA, Wong, TY, Saw, S-M, Parssinen, O, Stambolian, D, Hammond, CJ, Klaver, CCW, Williams, C, Paterson, AD, Bailey-Wilson, JE, and Guggenheim, JA

Abstract

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Published
2015

45. APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans

Author

Tkatchenko, AV, Tkatchenko, TV, Guggenheim, JA, Verhoeven, Virginie, Hysi, PG, Wojciechowski, R, Singh, PK, Kumar, A, Thinakaran, G, Williams, C, Tkatchenko, AV, Tkatchenko, TV, Guggenheim, JA, Verhoeven, Virginie, Hysi, PG, Wojciechowski, R, Singh, PK, Kumar, A, Thinakaran, G, and Williams, C

Published
2015

47. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia (vol 45, pg 314, 2013)

Author

Verhoeven, Virginie, Hysi, PG, Wojciechowski, R, Fan, Q, Guggenheim, JA, Hohn, R, Macgregor, S, Hewitt, AW, Nag, A, Cheng, CY (Ching-Yu), Yonova-Doing, E, Zhou, X, Ikram, Kamran, Buitendijk, Gabriëlle, McMahon, G, Kemp, JP, St Pourcain, B, Simpson, CL, Makela, KM, Lehtimaki, T, Kahonen, M, Paterson, AD, Hosseini, SM, Wong, HS, Xu, L, Jonas, JB, Parssinen, O, Wedenoja, J, Yip, SP, Ho, DWH, Pang, CP, Chen, LJ, Burdon, KP, Craig, JE, Klein, BEK, Klein, R, Haller, T, Metspalu, A, Khor, CC, Tai, ES, Aung, T, Vithana, E, Tay, WT, Barathi, VA, Chen, Peng, Li, RY, Liao, JM, Zheng, YF, Ong, RT, Doring, A, Evans, DM, Timpson, NJ, Verkerk, AJMH, Meitinger, T, Raitakari, O, Hawthorne, F, Spector, TD, Karssen, Lennart, Pirastu, M, Murgia, F, Ang, W, Mishra, A, Montgomery, GW, Pennell, CE, Cumberland, PM, Cotlarciuc, I, Mitchell, P, Wang, JJ, Schache, M, Janmahasathian, S, Igo, RP, Lass, JH, Chew, E, KIyengar, S, Gorgels, TGMF (Theo), Rudan, I, Hayward, C, Wright, AF, Polasek, O, Vatavuk, Z, Wilson, JF, Fleck, B, Zeller, T, Mirshahi, A, Müller, Caspar, Uitterlinden, André, Rivadeneira, Fernando, Vingerling, Hans, Hofman, Bert, Oostra, Ben, Amin, Najaf, Bergen, Arthur, Teo, YY, Rahi, JS, Vitart, V, Williams, C, Baird, PN, Wong, TY (Tien Yin), Oexle, K, Pfeiffer, N, Mackey, DA, Young, TL, Duijn, Cornelia, Saw, SM, Bailey-Wilson, JE, Stambolian, D, Klaver, Caroline, Hammond, CJ, Ophthalmology, Pathology, Epidemiology, Cell biology, Anesthesiology, Internal Medicine, Clinical Genetics, and Obstetrics & Gynecology

Published
2013

49. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Author

Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Aung, T. (Tin), Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), and Aung, T. (Tin)

Abstract

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10 '8 for rs6445055), two on chromosome 9 (P = 2.80 × 10 '11 for rs2472493 near ABCA1 and P = 6.39 × 10 '11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10 '11 for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

Published
2014
Full Text
View/download PDF

50. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Author

Simpson, C.L. (Claire), Wojciechowski, R. (Robert), Oexle, K. (Konrad), Murgia, D. (Daniela), Portas, L. (Laura), Li, X. (Xiaohui), Virginie, J.M.V. (J.M. Verhoeven), Vitart, V. (Veronique), Schache, M. (Maria), Mohsen Hosseini, S., Hysi, P.G. (Pirro), Raffel, L.J. (Leslie), Cotch, M.F. (Mary Frances), Chew, E.Y. (Emily), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, T.Y. (Tien Yin), Duijn, C.M. (Cornelia) van, Mitchell, P. (Paul), Saw, S-M. (Seang-Mei), Fossarello, M. (Maurizio), Wang, J.J. (Jie Jin), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Amin, N. (Najaf), Karssen, L.C. (Lennart), Vingerling, J.R. (Hans), Döring, A. (Angela), Bettecken, T. (Thomas), Bencic, G. (Goran), Gieger, C. (Christian), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Venturini, C. (Cristina), Fleck, B. (Brian), Cumberland, P. (Phillippa), Rahi, J.S. (Jugnoo), Hammond, C.J. (Christopher), Hayward, C. (Caroline), Wright, A. (Alan), Paterson, A.D. (Andrew), Baird, P.N. (Paul), Klaver, C.C.W. (Caroline), Rotter, J.I. (Jerome I.), Pirastu, M. (Mario), Meitinger, T. (Thomas), Bailey-Wilson, J.E. (Joan E.), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wojciechowski, R. (Robert), Oexle, K. (Konrad), Murgia, D. (Daniela), Portas, L. (Laura), Li, X. (Xiaohui), Virginie, J.M.V. (J.M. Verhoeven), Vitart, V. (Veronique), Schache, M. (Maria), Mohsen Hosseini, S., Hysi, P.G. (Pirro), Raffel, L.J. (Leslie), Cotch, M.F. (Mary Frances), Chew, E.Y. (Emily), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, T.Y. (Tien Yin), Duijn, C.M. (Cornelia) van, Mitchell, P. (Paul), Saw, S-M. (Seang-Mei), Fossarello, M. (Maurizio), Wang, J.J. (Jie Jin), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Amin, N. (Najaf), Karssen, L.C. (Lennart), Vingerling, J.R. (Hans), Döring, A. (Angela), Bettecken, T. (Thomas), Bencic, G. (Goran), Gieger, C. (Christian), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Venturini, C. (Cristina), Fleck, B. (Brian), Cumberland, P. (Phillippa), Rahi, J.S. (Jugnoo), Hammond, C.J. (Christopher), Hayward, C. (Caroline), Wright, A. (Alan), Paterson, A.D. (Andrew), Baird, P.N. (Paul), Klaver, C.C.W. (Caroline), Rotter, J.I. (Jerome I.), Pirastu, M. (Mario), Meitinger, T. (Thomas), Bailey-Wilson, J.E. (Joan E.), and Stambolian, D.E. (Dwight)

Abstract

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25610-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genomewide significant associations

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results