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1. 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
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2. Meta-analysis of human genome-microbiome association studies: The MiBioGen consortium initiative

Author

Wang, J. (Jun), Kurilshikov, A. (Alexander), Radjabzadeh, D. (Djawad), Turpin, W. (Williams), Croitoru, K. (Kenneth), Bonder, M.J. (Marc), Jackson, M.A. (Matthew A.), Medina-Gomez, M.C. (Carolina), Frost, F. (Fabian), Homuth, G. (Georg), Rühlemann, M. (Malte), Hughes, D. (David), Kim, H.-N. (Han-na), Spector, T.D. (Timothy), Bell, J.T. (Jordana T.), Steves, C.J. (Claire), Timpson, N. (Nicolas), Franke, A. (Andre), Wijmenga, C. (Cisca), Meyer, K. (Katie), Kacprowski, T. (Tim), Franke, L. (Lude), Paterson, A.D. (Andrew), Raes, J. (Jeroen), Kraaij, R. (Robert), Zhernakova, A. (Alexandra), Wang, J. (Jun), Kurilshikov, A. (Alexander), Radjabzadeh, D. (Djawad), Turpin, W. (Williams), Croitoru, K. (Kenneth), Bonder, M.J. (Marc), Jackson, M.A. (Matthew A.), Medina-Gomez, M.C. (Carolina), Frost, F. (Fabian), Homuth, G. (Georg), Rühlemann, M. (Malte), Hughes, D. (David), Kim, H.-N. (Han-na), Spector, T.D. (Timothy), Bell, J.T. (Jordana T.), Steves, C.J. (Claire), Timpson, N. (Nicolas), Franke, A. (Andre), Wijmenga, C. (Cisca), Meyer, K. (Katie), Kacprowski, T. (Tim), Franke, L. (Lude), Paterson, A.D. (Andrew), Raes, J. (Jeroen), Kraaij, R. (Robert), and Zhernakova, A. (Alexandra)

Abstract

Background: In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Results: Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. Conclusion: We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

Published
2018
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3. 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
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4. 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
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5. 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
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6. 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
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7. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Arking, D.E. (Dan), Pulit, S.L. (Sara), Crotti, L. (Lia), Harst, P. (Pim) van der, Munroe, P. (Patricia), Koopmann, T.T. (Tamara), Sotoodehnia, N. (Nona), Rossin, E. (Elizabeth), Morley, M. (Michael), Wang, X. (Xinchen), Johnson, A.D. (Andrew), Lundby, A. (Alicia), Gudbjartsson, D.F. (Daniel), Noseworthy, P.A. (Peter), Eijgelsheim, M. (Mark), Bradford, Y. (Yuki), Tarasov, K.V. (Kirill), Dörr, M. (Marcus), Müller-Nurasyid, M. (Martina), Lahtinen, A.M. (Annukka), Nolte, I.M. (Ilja), Smith, A.V. (Davey), Bis, J.C. (Joshua), Isaacs, A.J. (Aaron), Newhouse, S.J. (Stephen), Evans, D.S. (Daniel), Post, W.S. (Wendy S.), Waggott, D. (Daryl), Lyytikäinen, L.-P. (Leo-Pekka), Hicks, A.A. (Andrew), Eisele, L. (Lewin), Ellinghaus, D. (David), Hayward, C. (Caroline), Navarro, P. (Pau), Ulivi, S. (Shelia), Tanaka, T. (Toshiko), Tester, D.J. (David), Chatel, S. (Stéphanie), Gustafsson, S. (Stefan), Kumari, M. (Meena), Morris, R.W. (Richard), Naluai, A.T. (Asa), Padmanabhan, S. (Sandosh), Kluttig, A. (Alexander), Strohmer, B. (Bernhard), Panayiotou, A.G. (Andrie), Torres, M. (Maria), Knoflach, M. (Michael), Hubacek, J.A. (Jaroslav A.), Slowikowski, K. (Kamil), Raychaudhuri, S. (Soumya), Kumar, R.D. (Runjun), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Shuldiner, A.R. (Alan), Alonso, A. (Alvaro), Bader, J.S. (Joel), Ehret, G.B. (Georg), Huang, H. (Hailiang), Kao, W.H.L. (Wen), Strait, J.B. (James), Macfarlane, P.W. (Peter), Brown, M.J. (Morris), Caulfield, M. (Mark), Samani, N.J. (Nilesh), Kronenberg, F. (Florian), Willeit, J. (Johann), Smith, J.G. (J. Gustav), Greiser, K.H. (Karin Halina), Zu Schwabedissen, H.M. (Henriette Meyer), Werdan, K. (Karl), Carella, C. (Cintia), Zelante, L. (Leopoldo), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), Kolcic, I. (Ivana), Polasek, O. (Ozren), Wright, A.F. (Alan), Griffin, M. (Maura), Daly, M.J. (Mark), Arnar, D.O. (David), Hólm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Denny, J.C. (Joshua), Roden, D.M. (Dan), Zuvich, R.L. (Rebecca), Emilsson, V. (Valur), Plump, A.S. (Andrew), Larson, M.G. (Martin), O'Donnell, C.J. (Christopher), Yin, X. (Xiaoyan), Bobbo, M. (Marco), Adamo, P. (Pio) d', Iorio, A. (Annamaria), Sinagra, G. (Gianfranco), Carracedo, A. (Angel), Cummings, S.R. (Steven), Nalls, M.A. (Michael), Jula, A. (Antti), Kontula, K.K. (Kimmo), Marjamaa, A. (Annukka), Oikarinen, L. (Lasse), Perola, M. (Markus), Porthan, K. (Kimmo), Erbel, R. (Raimund), Hoffmann, P. (Per), Jöckel, K.-H. (Karl-Heinz), Kälsch, H. (Hagen), Nöthen, M.M. (Markus), Hoed, M. (Marcel) den, Loos, R.J.F. (Ruth), Thelle, D.S. (Dag), Gieger, C. (Christian), Meitinger, T. (Thomas), Perz, S. (Siegfried), Peters, A. (Annette), Prucha, H. (Hanna), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Boer, R.A. (Rudolf) de, Franke, L. (Lude), Vleuten, P.A. (Pieter) van der, Beckmann, B.M. (Britt), Martens, E. (Eimo), Bardai, A. (Abdennasser), Hofman, N. (Nynke), Wilde, A.A.M. (Arthur), Behr, E.R. (Elijah), Dalageorgou, C. (Chrysoula), Giudicessi, J.R. (John), Medeiros-Domingo, A. (Argelia), Barc, J. (Julien), Kyndt, F. (Florence), Probst, V. (Vincent), Ghidoni, A. (Alice), Insolia, R. (Roberto), Hamilton, R.M. (Robert), Scherer, S.W. (Stephen), Brandimarto, J. (Jeffrey), Margulies, K. (Kenneth), Moravec, C.E. (Christine), Del Greco, F. (Fabiola), Fuchsberger, C. (Christian), O'Connell, J.R. (Jeffery), Lee, W.K. (Wai), Watt, G.C.M. (Graham), Campbell, H. (Harry), Wild, S.H. (Sarah), El Mokhtari, N.E. (Nour), Frey, N. (Norbert), Asselbergs, F.W. (Folkert), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Berg, M.P. (Maarten) van den, Veldhuisen, D.J. (Dirk) van, Kellis, M. (Manolis), Krijthe, B.P. (Bouwe), Franco, O.H. (Oscar), Hofman, A. (Albert), Kors, J.A. (Jan), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Kedenko, L. (Lyudmyla), Lamina, C. (Claudia), Oostra, B.A. (Ben), Abecasis, G.R. (Gonçalo), Lakatta, E. (Edward), Mulas, A. (Antonella), Orrù, M. (Marco), Schlessinger, D. (David), Uda, M. (Manuela), Markus, M.R.P. (Marcello R. P.), Völker, U. (Uwe), Snieder, H. (Harold), Spector, T.D. (Timothy), Ärnlöv, J. (Johan), Lind, L. (Lars), Sundstrom, J. (Johan), Syvanen, A.C., Kivimaki, M. (Mika), Kähönen, M. (Mika), Mononen, K. (Kari), Raitakari, O. (Olli), Viikari, J. (Jorma), Adamkova, V. (Vera), Kiechl, S. (Stefan), Brion, M.-J. (Maria), Nicolaides, A.N. (Andrew), Paulweber, B. (Bernhard), Haerting, J. (Johannes), Dominiczak, A. (Anna), Nyberg, F. (Fredrik), Whincup, P.H. (Peter), Hingorani, A. (Aroon), Schott, J.-J. (Jean-Jacques), Bezzina, C.R. (Connie), Ingelsson, E. (Erik), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Wilson, J.F. (James), Rudan, I. (Igor), Franke, A. (Andre), Mühleisen, T.W. (Thomas), Pramstaller, P.P. (Peter Paul), Lehtimäki, T. (Terho), Paterson, A.D. (Andrew), Parsa, A. (Afshin), Liu, Y. (YongMei), Duijn, C.M. (Cornelia) van, Siscovick, D.S. (David), Gudnason, V. (Vilmundur), Jamshidi, Y. (Yalda), Salomaa, V. (Veikko), Felix, S.B. (Stephan), Sanna, S. (Serena), Ritchie, M.D. (Marylyn), Stricker, B.H.Ch. (Bruno), Zwart, J-A. (John-Anker), Boyer, L.A. (Laurie), Cappola, T.P. (Thomas), Olsen, J.V. (Jesper), Lage, P. (Pedro), Schwartz, P.J. (Peter), Kääb, S. (Stefan), Chakravarti, A. (Aravinda), Ackerman, M. (Margaret), Pfeufer, A. (Arne), Bakker, P.I.W. (Paul) de, Newton-Cheh, C. (Christopher), Arking, D.E. (Dan), Pulit, S.L. (Sara), Crotti, L. (Lia), Harst, P. (Pim) van der, Munroe, P. (Patricia), Koopmann, T.T. (Tamara), Sotoodehnia, N. (Nona), Rossin, E. (Elizabeth), Morley, M. (Michael), Wang, X. (Xinchen), Johnson, A.D. (Andrew), Lundby, A. (Alicia), Gudbjartsson, D.F. (Daniel), Noseworthy, P.A. (Peter), Eijgelsheim, M. (Mark), Bradford, Y. (Yuki), Tarasov, K.V. (Kirill), Dörr, M. (Marcus), Müller-Nurasyid, M. (Martina), Lahtinen, A.M. (Annukka), Nolte, I.M. (Ilja), Smith, A.V. (Davey), Bis, J.C. (Joshua), Isaacs, A.J. (Aaron), Newhouse, S.J. (Stephen), Evans, D.S. (Daniel), Post, W.S. (Wendy S.), Waggott, D. (Daryl), Lyytikäinen, L.-P. (Leo-Pekka), Hicks, A.A. (Andrew), Eisele, L. (Lewin), Ellinghaus, D. (David), Hayward, C. (Caroline), Navarro, P. (Pau), Ulivi, S. (Shelia), Tanaka, T. (Toshiko), Tester, D.J. (David), Chatel, S. (Stéphanie), Gustafsson, S. (Stefan), Kumari, M. (Meena), Morris, R.W. (Richard), Naluai, A.T. (Asa), Padmanabhan, S. (Sandosh), Kluttig, A. (Alexander), Strohmer, B. (Bernhard), Panayiotou, A.G. (Andrie), Torres, M. (Maria), Knoflach, M. (Michael), Hubacek, J.A. (Jaroslav A.), Slowikowski, K. (Kamil), Raychaudhuri, S. (Soumya), Kumar, R.D. (Runjun), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Shuldiner, A.R. (Alan), Alonso, A. (Alvaro), Bader, J.S. (Joel), Ehret, G.B. (Georg), Huang, H. (Hailiang), Kao, W.H.L. (Wen), Strait, J.B. (James), Macfarlane, P.W. (Peter), Brown, M.J. (Morris), Caulfield, M. (Mark), Samani, N.J. (Nilesh), Kronenberg, F. (Florian), Willeit, J. (Johann), Smith, J.G. (J. Gustav), Greiser, K.H. (Karin Halina), Zu Schwabedissen, H.M. (Henriette Meyer), Werdan, K. (Karl), Carella, C. (Cintia), Zelante, L. (Leopoldo), Heckbert, S.R. (Susan), Psaty, B.M. (Bruce), Rotter, J.I. (Jerome), Kolcic, I. (Ivana), Polasek, O. (Ozren), Wright, A.F. (Alan), Griffin, M. (Maura), Daly, M.J. (Mark), Arnar, D.O. (David), Hólm, H. (Hilma), Thorsteinsdottir, U. (Unnur), Denny, J.C. (Joshua), Roden, D.M. (Dan), Zuvich, R.L. (Rebecca), Emilsson, V. (Valur), Plump, A.S. (Andrew), Larson, M.G. (Martin), O'Donnell, C.J. (Christopher), Yin, X. (Xiaoyan), Bobbo, M. (Marco), Adamo, P. (Pio) d', Iorio, A. (Annamaria), Sinagra, G. (Gianfranco), Carracedo, A. (Angel), Cummings, S.R. (Steven), Nalls, M.A. (Michael), Jula, A. (Antti), Kontula, K.K. (Kimmo), Marjamaa, A. (Annukka), Oikarinen, L. (Lasse), Perola, M. (Markus), Porthan, K. (Kimmo), Erbel, R. (Raimund), Hoffmann, P. (Per), Jöckel, K.-H. (Karl-Heinz), Kälsch, H. (Hagen), Nöthen, M.M. (Markus), Hoed, M. (Marcel) den, Loos, R.J.F. (Ruth), Thelle, D.S. (Dag), Gieger, C. (Christian), Meitinger, T. (Thomas), Perz, S. (Siegfried), Peters, A. (Annette), Prucha, H. (Hanna), Sinner, M.F. (Moritz), Waldenberger, M. (Melanie), Boer, R.A. (Rudolf) de, Franke, L. (Lude), Vleuten, P.A. (Pieter) van der, Beckmann, B.M. (Britt), Martens, E. (Eimo), Bardai, A. (Abdennasser), Hofman, N. (Nynke), Wilde, A.A.M. (Arthur), Behr, E.R. (Elijah), Dalageorgou, C. (Chrysoula), Giudicessi, J.R. (John), Medeiros-Domingo, A. (Argelia), Barc, J. (Julien), Kyndt, F. (Florence), Probst, V. (Vincent), Ghidoni, A. (Alice), Insolia, R. (Roberto), Hamilton, R.M. (Robert), Scherer, S.W. (Stephen), Brandimarto, J. (Jeffrey), Margulies, K. (Kenneth), Moravec, C.E. (Christine), Del Greco, F. (Fabiola), Fuchsberger, C. (Christian), O'Connell, J.R. (Jeffery), Lee, W.K. (Wai), Watt, G.C.M. (Graham), Campbell, H. (Harry), Wild, S.H. (Sarah), El Mokhtari, N.E. (Nour), Frey, N. (Norbert), Asselbergs, F.W. (Folkert), Leach, I.M. (Irene Mateo), Navis, G. (Gerjan), Berg, M.P. (Maarten) van den, Veldhuisen, D.J. (Dirk) van, Kellis, M. (Manolis), Krijthe, B.P. (Bouwe), Franco, O.H. (Oscar), Hofman, A. (Albert), Kors, J.A. (Jan), Uitterlinden, A.G. (André), Witteman, J.C.M. (Jacqueline), Kedenko, L. (Lyudmyla), Lamina, C. (Claudia), Oostra, B.A. (Ben), Abecasis, G.R. (Gonçalo), Lakatta, E. (Edward), Mulas, A. (Antonella), Orrù, M. (Marco), Schlessinger, D. (David), Uda, M. (Manuela), Markus, M.R.P. (Marcello R. P.), Völker, U. (Uwe), Snieder, H. (Harold), Spector, T.D. (Timothy), Ärnlöv, J. (Johan), Lind, L. (Lars), Sundstrom, J. (Johan), Syvanen, A.C., Kivimaki, M. (Mika), Kähönen, M. (Mika), Mononen, K. (Kari), Raitakari, O. (Olli), Viikari, J. (Jorma), Adamkova, V. (Vera), Kiechl, S. (Stefan), Brion, M.-J. (Maria), Nicolaides, A.N. (Andrew), Paulweber, B. (Bernhard), Haerting, J. (Johannes), Dominiczak, A. (Anna), Nyberg, F. (Fredrik), Whincup, P.H. (Peter), Hingorani, A. (Aroon), Schott, J.-J. (Jean-Jacques), Bezzina, C.R. (Connie), Ingelsson, E. (Erik), Ferrucci, L. (Luigi), Gasparini, P. (Paolo), Wilson, J.F. (James), Rudan, I. (Igor), Franke, A. (Andre), Mühleisen, T.W. (Thomas), Pramstaller, P.P. (Peter Paul), Lehtimäki, T. (Terho), Paterson, A.D. (Andrew), Parsa, A. (Afshin), Liu, Y. (YongMei), Duijn, C.M. (Cornelia) van, Siscovick, D.S. (David), Gudnason, V. (Vilmundur), Jamshidi, Y. (Yalda), Salomaa, V. (Veikko), Felix, S.B. (Stephan), Sanna, S. (Serena), Ritchie, M.D. (Marylyn), Stricker, B.H.Ch. (Bruno), Zwart, J-A. (John-Anker), Boyer, L.A. (Laurie), Cappola, T.P. (Thomas), Olsen, J.V. (Jesper), Lage, P. (Pedro), Schwartz, P.J. (Peter), Kääb, S. (Stefan), Chakravarti, A. (Aravinda), Ackerman, M. (Margaret), Pfeufer, A. (Arne), Bakker, P.I.W. (Paul) de, and Newton-Cheh, C. (Christopher)

Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Published
2014
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8. Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Author

Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Wojciechowski, R. (Robert), Fan, Q. (Qiao), Guggenheim, J. (Jean), Höhn, R. (René), MacGregor, S. (Stuart), Hewit, A.W. (Alex), Nag, A. (Abhishek), Cheng, C-Y. (Ching-Yu), Yonova-Doing, E. (Ekaterina), Zhou, X. (Xin), Ikram, M.K. (Kamran), Buitendijk, G.H.S. (Gabrielle), Mcmahon, G. (George), Kemp, J.P. (John), Pourcain, B.S. (Beate), Simpson, C.L. (Claire), Mäkelä, M.J., Lehtimäki, T. (Terho), Kähönen, M. (Mika), Paterson, A.D. (Andrew), Hosseini, M. (Mehran), Wong, H.S. (Hoi Suen), Xu, L. (Liang), Jonas, J.B., Pärssinen, O. (Olavi), Wedenoja, J. (Juho), Yip, S.P. (Shea Ping), Ho, D.W.H. (Daniel), Pang, C.P. (Chi), Chen, L.J. (Li), Burdon, K.P. (Kathryn), Craig, J.E. (Jamie), Klein, B.E.K. (Barbara), Haller, T. (Toomas), Metspalu, A. (Andres), Khor, C.C., Tai, E.S. (Shyong), Aung, T. (Tin), Vithana, E.N. (Eranga), Tay, W.-T. (Wan-Ting), Barathi, V.A. (Veluchamy), Chen, P. (Ping), Li, R. (Rui), Liao, J. (Jie), Zheng, Y. (Yuhui), Ong, R.T.H. (Rick Twee-Hee), Döring, A. (Angela), Evans, D.M. (David), Timpson, N.J. (Nicholas), Verkerk, A., Meitinger, T. (Thomas), Raitakari, O. (Olli), Hawthorne, F. (Felicia), Spector, T.D. (Timothy), Karssen, L.C. (Lennart), Pirastu, M. (Mario), Murgia, D. (Daniela), Ang, W.Q. (Wei), Mishra, A. (Aniket), Montgomery, G.W. (Grant), Pennell, C.E. (Craig), Cumberland, P. (Phillippa), Cotlarciuc, I. (Ioana), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Schache, M. (Maria), Janmahasathian, S. (Sarayut), Igo Jr., R.P. (Robert), Lass Jr., J.H. (Jonathan), Chew, E.Y. (Emily), Iyengar, S.K. (Sudha), Gorgels, T.G.M.F. (Theo), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Polasek, O. (Ozren), Vatavuk, Z. (Zoran), Wilson, J.F. (James), Fleck, B. (Brian), Zeller, T. (Tanja), Mirshahi, A. (Alireza), Müller, C. (Christian), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Vingerling, J.R. (Hans), Hofman, A. (Albert), Oostra, B.A. (Ben), Amin, N. (Najaf), Bergen, A.A.B. (Arthur), Teo, Y.Y. (Yik Ying), Rahi, J.S. (Jugnoo), Vitart, V. (Veronique), Williams, C. (Cathy), Baird, P.N. (Paul), Wong, T.Y. (Tien Yin), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Young, T.L. (Terri), Duijn, C.M. (Cornelia) van, Saw, S-M. (Seang-Mei), Bailey-Wilson, J.E. (Joan), Stambolian, D.E. (Dwight), Klaver, C.C.W. (Caroline), Hammond, C.J. (Christopher), Verhoeven, V.J.M. (Virginie), Hysi, P.G. (Pirro), Wojciechowski, R. (Robert), Fan, Q. (Qiao), Guggenheim, J. (Jean), Höhn, R. (René), MacGregor, S. (Stuart), Hewit, A.W. (Alex), Nag, A. (Abhishek), Cheng, C-Y. (Ching-Yu), Yonova-Doing, E. (Ekaterina), Zhou, X. (Xin), Ikram, M.K. (Kamran), Buitendijk, G.H.S. (Gabrielle), Mcmahon, G. (George), Kemp, J.P. (John), Pourcain, B.S. (Beate), Simpson, C.L. (Claire), Mäkelä, M.J., Lehtimäki, T. (Terho), Kähönen, M. (Mika), Paterson, A.D. (Andrew), Hosseini, M. (Mehran), Wong, H.S. (Hoi Suen), Xu, L. (Liang), Jonas, J.B., Pärssinen, O. (Olavi), Wedenoja, J. (Juho), Yip, S.P. (Shea Ping), Ho, D.W.H. (Daniel), Pang, C.P. (Chi), Chen, L.J. (Li), Burdon, K.P. (Kathryn), Craig, J.E. (Jamie), Klein, B.E.K. (Barbara), Haller, T. (Toomas), Metspalu, A. (Andres), Khor, C.C., Tai, E.S. (Shyong), Aung, T. (Tin), Vithana, E.N. (Eranga), Tay, W.-T. (Wan-Ting), Barathi, V.A. (Veluchamy), Chen, P. (Ping), Li, R. (Rui), Liao, J. (Jie), Zheng, Y. (Yuhui), Ong, R.T.H. (Rick Twee-Hee), Döring, A. (Angela), Evans, D.M. (David), Timpson, N.J. (Nicholas), Verkerk, A., Meitinger, T. (Thomas), Raitakari, O. (Olli), Hawthorne, F. (Felicia), Spector, T.D. (Timothy), Karssen, L.C. (Lennart), Pirastu, M. (Mario), Murgia, D. (Daniela), Ang, W.Q. (Wei), Mishra, A. (Aniket), Montgomery, G.W. (Grant), Pennell, C.E. (Craig), Cumberland, P. (Phillippa), Cotlarciuc, I. (Ioana), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Schache, M. (Maria), Janmahasathian, S. (Sarayut), Igo Jr., R.P. (Robert), Lass Jr., J.H. (Jonathan), Chew, E.Y. (Emily), Iyengar, S.K. (Sudha), Gorgels, T.G.M.F. (Theo), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Polasek, O. (Ozren), Vatavuk, Z. (Zoran), Wilson, J.F. (James), Fleck, B. (Brian), Zeller, T. (Tanja), Mirshahi, A. (Alireza), Müller, C. (Christian), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Vingerling, J.R. (Hans), Hofman, A. (Albert), Oostra, B.A. (Ben), Amin, N. (Najaf), Bergen, A.A.B. (Arthur), Teo, Y.Y. (Yik Ying), Rahi, J.S. (Jugnoo), Vitart, V. (Veronique), Williams, C. (Cathy), Baird, P.N. (Paul), Wong, T.Y. (Tien Yin), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Young, T.L. (Terri), Duijn, C.M. (Cornelia) van, Saw, S-M. (Seang-Mei), Bailey-Wilson, J.E. (Joan), Stambolian, D.E. (Dwight), Klaver, C.C.W. (Caroline), and Hammond, C.J. (Christopher)

Abstract

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

Published
2013
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9. Common genetic determinants of intraocular pressure and primary open-angle Glaucoma

Author

Koolwijk, L.M.E. (Leonieke) van, Ramdas, W.D. (Wishal), Ikram, M.K. (Kamran), Jansonius, N.M. (Nomdo), Pasutto, F. (Francesca), Hysi, P.G. (Pirro), MacGregor, S. (Stuart), Janssen, S.F. (Sarah), Hewit, A.W. (Alex), Viswanathan, A.C. (Ananth), Brink, J.B. (Jacoline) ten, Hosseini, M. (Mehran), Amin, N. (Najaf), Despriet, D.D.G. (Dominique), Willemse-Assink, J.J.M. (Jacqueline), Kramer, R. (Rogier), Rivadeneira Ramirez, F. (Fernando), Struchalin, M.V. (Maksim), Aulchenko, Y.S. (Yurii), Weisschuh, N. (Nicole), Zenkel, M. (Matthias), Mardin, C.Y. (Christian), Gramer, E. (Eugen), Welge-Lüssen, U. (Ulrich), Montgomery, G.W. (Grant), Carbonaro, F. (Francis), Young, T.L. (Terri), Bellenguez, C. (Céline), Mcguffin, P. (Peter), Foster, P.J. (Paul), Topouzis, F. (Fotis), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Wong, T.Y. (Tien Yin), Czudowska, M.A. (Monika), Hofman, A. (Albert), Uitterlinden, A.G. (André), Wolfs, R.C.W. (Roger), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Paterson, A.D. (Andrew), Mackey, D.A. (David), Bergen, A.A.B. (Arthur), Reis, A. (André), Hammond, C.J. (Christopher), Vingerling, J.R. (Hans), Lemij, H.G. (Hans), Klaver, C.C.W. (Caroline), Duijn, C.M. (Cornelia) van, Koolwijk, L.M.E. (Leonieke) van, Ramdas, W.D. (Wishal), Ikram, M.K. (Kamran), Jansonius, N.M. (Nomdo), Pasutto, F. (Francesca), Hysi, P.G. (Pirro), MacGregor, S. (Stuart), Janssen, S.F. (Sarah), Hewit, A.W. (Alex), Viswanathan, A.C. (Ananth), Brink, J.B. (Jacoline) ten, Hosseini, M. (Mehran), Amin, N. (Najaf), Despriet, D.D.G. (Dominique), Willemse-Assink, J.J.M. (Jacqueline), Kramer, R. (Rogier), Rivadeneira Ramirez, F. (Fernando), Struchalin, M.V. (Maksim), Aulchenko, Y.S. (Yurii), Weisschuh, N. (Nicole), Zenkel, M. (Matthias), Mardin, C.Y. (Christian), Gramer, E. (Eugen), Welge-Lüssen, U. (Ulrich), Montgomery, G.W. (Grant), Carbonaro, F. (Francis), Young, T.L. (Terri), Bellenguez, C. (Céline), Mcguffin, P. (Peter), Foster, P.J. (Paul), Topouzis, F. (Fotis), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Wong, T.Y. (Tien Yin), Czudowska, M.A. (Monika), Hofman, A. (Albert), Uitterlinden, A.G. (André), Wolfs, R.C.W. (Roger), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Paterson, A.D. (Andrew), Mackey, D.A. (David), Bergen, A.A.B. (Arthur), Reis, A. (André), Hammond, C.J. (Christopher), Vingerling, J.R. (Hans), Lemij, H.G. (Hans), Klaver, C.C.W. (Caroline), and Duijn, C.M. (Cornelia) van

Abstract

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a geno

Published
2012
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10. STrengthening the REporting of Genetic Association studies (STREGA) - An extension of the STROBE statement

Author

Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y. (Guang Yong), Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), Birkett, N. (Nick), Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y. (Guang Yong), Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), and Birkett, N. (Nick)

Abstract

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct or analysis.

Published
2009
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11. STrengthening the REporting of genetic association studies (STREGA)-an extension of the strobe statement

Author

Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y., Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), Birkett, N. (Nick), Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y., Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), and Birkett, N. (Nick)

Abstract

Summary Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic assoc

Published
2009
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12. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation

Author

Nolte, I.M. (Ilja), Wallace, C. (Chris), Newhouse, S.J. (Stephen), Waggott, D. (Daryl), Fu, J. (Jingyuan), Soranzo, N. (Nicole), Gwilliam, R. (Rhian), Demissie, S. (Serkalem), Savelieva, I. (Irina), Zheng, D. (Dongling), Dalageorgou, C. (Chrysoula), Farrall, M. (Martin), Samani, N.J. (Nilesh), Connell, J. (John), Brown, M.J. (Morris), Dominiczak, A. (Anna), Lathrop, M. (Mark), Zeggini, E. (Eleftheria), Wain, L.V. (Louise), Newton-Cheh, C. (Christopher), Eijgelsheim, M. (Mark), Rice, K. (Kenneth), Bakker, P.I.W. (Paul) de, Pfeufer, A. (Arne), Sanna, S. (Serena), Arking, D.E. (Dan), Asselbergs, F.W. (Folkert), Spector, T.D. (Timothy), Carter, N.D. (Nicholas), Jeffery, S. (Steve), Tobin, M. (Martin), Caulfield, M. (Mark), Snieder, H. (Harold), Paterson, A.D. (Andrew), Munroe, P. (Patricia), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja), Wallace, C. (Chris), Newhouse, S.J. (Stephen), Waggott, D. (Daryl), Fu, J. (Jingyuan), Soranzo, N. (Nicole), Gwilliam, R. (Rhian), Demissie, S. (Serkalem), Savelieva, I. (Irina), Zheng, D. (Dongling), Dalageorgou, C. (Chrysoula), Farrall, M. (Martin), Samani, N.J. (Nilesh), Connell, J. (John), Brown, M.J. (Morris), Dominiczak, A. (Anna), Lathrop, M. (Mark), Zeggini, E. (Eleftheria), Wain, L.V. (Louise), Newton-Cheh, C. (Christopher), Eijgelsheim, M. (Mark), Rice, K. (Kenneth), Bakker, P.I.W. (Paul) de, Pfeufer, A. (Arne), Sanna, S. (Serena), Arking, D.E. (Dan), Asselbergs, F.W. (Folkert), Spector, T.D. (Timothy), Carter, N.D. (Nicholas), Jeffery, S. (Steve), Tobin, M. (Martin), Caulfield, M. (Mark), Snieder, H. (Harold), Paterson, A.D. (Andrew), Munroe, P. (Patricia), and Jamshidi, Y. (Yalda)

Abstract

To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1×10-6. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4×10-83) and the phospholamban (PLN) gene (P = 1.9×10-29). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death.

Published
2009
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13. STrengthening the REporting of genetic association studies (STREGA)- An extension of the STROBE statement

Author

Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y., Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), Birkett, N. (Nick), Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y., Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), and Birkett, N. (Nick)

Abstract

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Published
2009
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14. Strengthening the reporting of genetic association studies (STREGA): An extension of the STROBE statement

Author

Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y., Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), Birkett, N. (Nick), Little, J. (Julian), Higgins, J.P.T. (Julian), Ioannidis, J.P.A. (John), Moher, D. (David), Gagnon, F. (France), Elm, E. (Erik) von, Khoury, M.J. (Muin Joseph), Cohen, B. (Barbara), Davey-Smith, G. (George), Grimshaw, J. (Jeremy), Scheet, P. (Paul), Gwinn, M. (Marta), Williamson, R.E. (Robin), Zou, G.Y., Hutchings, K. (Kim), Johnson, C.Y. (Candice), Tait, V. (Valerie), Wiens, M. (Miriam), Golding, J. (Jean), Duijn, C.M. (Cornelia) van, McLaughlin, J. (John), Paterson, A.D. (Andrew), Wells, G.A. (George), Fortier, I. (Isabel), Freedman, M. (Matthew), Zecevic, M. (Maja), King, R. (Richard), Infante-Rivard, C. (Claire), Stewart, A.F.R. (Alexandre), and Birkett, N. (Nick)

Abstract

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Published
2009
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