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

van Leeuwen, Em M.; van Koolwijk, Lm M.; de Jong, Pt T.; van Duijn, Cm M.; Hysi, Pg G.; Cheng, Cy-Y.; Cooke Bailey, Jessica N.; Springelkamp, Henriët; Hewitt, Aw W.; Zeller, Tanja; Macgregor, Stuart; Höhn, René; Pg, Hysi; Wang, Y. X.; Thorleifsson, Gudmar; Zheng, Yingfeng; Bailey, Jn N. C.; Ramdas, Wd D.; Xu, Liang; Vithana, Eranga; Wojciechowski, Robert; Stefansson, Arni B.; Khor, Cc-C.; Cy, Cheng; Liao, Jiemin; Vitart, Veronique; Amin, Najaf; Haines, Jl L.; Yazar, Seyhan; Nag, Abhishek; Ozel, Ayse B.; Wild, Ps S.; Li, Jz Z.; Fleck, Bw W.; Staffieri, Se E.; Teo, Yy-Y.; Wang, Yx X.; Cuellar-Partida, Gabriel; Luo, Xiaoyan; Wolfs, Rc C. W.; Venturini, Cristina; Allingham, Rr Rand; Young, Tl L.; Richards, Je E.; Mirshahi, Alireza; Senft, Andrea; Karssen, Lc C.; Bellenguez, Céline; Iglesias, Ai I.; Wilson, Jf F.; Kang, Jh H.; Wong, Ty-Y.; Van Leeuwen, E. M.; Jnc, Bailey; Jonsson, Vesteinn; Rand Allingham, R.; Thorsteinsdottir, Unnur; Despriet, Dominiek D. G.; Ennis, Sarah; Moroi, Se E.; Martin, Ng G.; Jansonius, Nm M.; Hohn, Rene; Tai, Es-Shyong; Amouyel, Philippe; Kirwan, James; Van Koolwijk, L. M. E.; Leeuwen, Elisabeth M. van; Hauser, Michael A.; Jonasson, Fridbert; Leo, Paul; Loomis, Sj J.; Fogarty, Rhys; Rivadeneira, Fernando; Kearns, Lisa; Wong, T.-Y.; Lackner, Kj J.; De Jong, P. T. V. M.; Simpson, Cl L.; Pennell, Ce E.; Shyong Tai, E.; Oostra, Ben A.; Uitterlinden, Ag G.; Wang, J. J.; Saw, Sm-M.; Rochtchina, E.; Lotery, Aj J.; Attia, J.; Bailey-Wilson, Je E.; Scott, R.; Koolwijk, Leonieke M. E. van; Hofman, Albert; Holliday, E. G.; Vingerling, Johannes R.; Baird, P. N.; Maubaret, Cécilia; Xie, J.; Pfeiffer, Norbert; Inouye, M.; Lemij, Hg G.; Sim, X.; Brilliant, M. H.; Pasquale, Lr R.; Budenz, D. L.; Aw, Hewitt; Delcourt, Cécile; Christen, W. G.; Spector, Td D.; Fingert, J.; Friedman, D. S.; Klaver, Cc C. W.; Gaasterland, D.; Small, Ks S.; Gaasterland, T.; Kang, J. H.; Burdon, Kp P.; Kraft, P.; Stefansson, Kari; Lee, R. K.; Jong, Paulus T. V. M. de; Lichter, P. A.; Liu, Y.; Pericak-Vance,; Viswanathan, Ananth; Realini, A.; Schuman, J. S.; Mackey, Da A.; Scott, W. K.; Craig, Je E.; Singh, K.; Wiggs, Jl L.; Sit, A. J.; Van Duijn, C. M.; Vollrath, D.; Hammond, Cj J.; Weinreb,; Aung, Tin; Wollstein, G.; Zack, D. J.; Zhang, K.; Donnelly, P.; Barroso, I.; Blackwell, J. M.; Bramon, E.; Brown,; Casas, J. P.; Corvin, A.; Deloukas, P.; Gillman, M.; Gray, E.; Markus, H. S.; Group, Bmes Gwas; Mathew, C. G.; McCann, O. T.; Liddle, J.; Potter, S. C.; Consortium, Neighborhood; Ravindrarajah, R.; 2., Wellcome Trust Case Control Consortium; Ricketts, M.; Wd, Ramdas; Waller, M.; Wood, N. W.; Spencer, C. C. A.; Ao, David Mackey; Band, G.; Freeman, C.; Hellenthal, G.; Giannoulatou, E.; Pirinen, M.; Pearson, R.; Strange, A.; Su, Z.; Vukcevic, D.

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Ching-Yu Cheng
van Leeuwen et al., 2014

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Nature Research, Nature Genetics, 10(46), p. 1126-1130, 2014

DOI: 10.1038/ng.3087

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@article{van Leeuwen2014,
  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.},
  author = {van Leeuwen, Em M. and van Koolwijk, Lm M. and de Jong, Pt T. and van Duijn, Cm M. and Hysi, Pg G. and Cheng, Cy-Y. and Cooke Bailey, Jessica N. and Springelkamp, Henriët and Hewitt, Aw W. and Zeller, Tanja and Macgregor, Stuart and Höhn, René and Pg, Hysi and Wang, Y. X. and Thorleifsson, Gudmar and Zheng, Yingfeng and Bailey, Jn N. C. and Ramdas, Wd D. and Xu, Liang and Vithana, Eranga and Wojciechowski, Robert and Stefansson, Arni B. and Khor, Cc-C. and Cy, Cheng and Liao, Jiemin and Vitart, Veronique and Amin, Najaf and Haines, Jl L. and Yazar, Seyhan and Nag, Abhishek and Ozel, Ayse B. and Wild, Ps S. and Li, Jz Z. and Fleck, Bw W. and Staffieri, Se E. and Teo, Yy-Y. and Wang, Yx X. and Cuellar-Partida, Gabriel and Luo, Xiaoyan and Wolfs, Rc C. W. and Venturini, Cristina and Allingham, Rr Rand and Young, Tl L. and Richards, Je E. and Mirshahi, Alireza and Senft, Andrea and Karssen, Lc C. and Bellenguez, Céline and Iglesias, Ai I. and Wilson, Jf F. and Kang, Jh H. and Wong, Ty-Y. and Van Leeuwen, E. M. and Jnc, Bailey and Jonsson, Vesteinn and Rand Allingham, R. and Thorsteinsdottir, Unnur and Despriet, Dominiek D. G. and Ennis, Sarah and Moroi, Se E. and Martin, Ng G. and Jansonius, Nm M. and Hohn, Rene and Tai, Es-Shyong and Amouyel, Philippe and Kirwan, James and Van Koolwijk, L. M. E. and Leeuwen, Elisabeth M. van and Hauser, Michael A. and Jonasson, Fridbert and Leo, Paul and Loomis, Sj J. and Fogarty, Rhys and Rivadeneira, Fernando and Kearns, Lisa and Wong, T.-Y. and Lackner, Kj J. and De Jong, P. T. V. M. and Simpson, Cl L. and Pennell, Ce E. and Shyong Tai, E. and Oostra, Ben A. and Uitterlinden, Ag G. and Wang, J. J. and Saw, Sm-M. and Rochtchina, E. and Lotery, Aj J. and Attia, J. and Bailey-Wilson, Je E. and Scott, R. and Koolwijk, Leonieke M. E. van and Hofman, Albert and Holliday, E. G. and Vingerling, Johannes R. and Baird, P. N. and Maubaret, Cécilia and Xie, J. and Pfeiffer, Norbert and Inouye, M. and Lemij, Hg G. and Sim, X. and Brilliant, M. H. and Pasquale, Lr R. and Budenz, D. L. and Aw, Hewitt and Delcourt, Cécile and Christen, W. G. and Spector, Td D. and Fingert, J. and Friedman, D. S. and Klaver, Cc C. W. and Gaasterland, D. and Small, Ks S. and Gaasterland, T. and Kang, J. H. and Burdon, Kp P. and Kraft, P. and Stefansson, Kari and Lee, R. K. and Jong, Paulus T. V. M. de and Lichter, P. A. and Liu, Y. and Pericak-Vance,  and Viswanathan, Ananth and Realini, A. and Schuman, J. S. and Mackey, Da A. and Scott, W. K. and Craig, Je E. and Singh, K. and Wiggs, Jl L. and Sit, A. J. and Van Duijn, C. M. and Vollrath, D. and Hammond, Cj J. and Weinreb,  and Aung, Tin and Wollstein, G. and Zack, D. J. and Zhang, K. and Donnelly, P. and Barroso, I. and Blackwell, J. M. and Bramon, E. and Brown,  and Casas, J. P. and Corvin, A. and Deloukas, P. and Gillman, M. and Gray, E. and Markus, H. S. and Group, Bmes Gwas and Mathew, C. G. and McCann, O. T. and Liddle, J. and Potter, S. C. and Consortium, Neighborhood and Ravindrarajah, R. and 2., Wellcome Trust Case Control Consortium and Ricketts, M. and Wd, Ramdas and Waller, M. and Wood, N. W. and Spencer, C. C. A. and Ao, David Mackey and Band, G. and Freeman, C. and Hellenthal, G. and Giannoulatou, E. and Pirinen, M. and Pearson, R. and Strange, A. and Su, Z. and Vukcevic, D.},
  doi = {10.1038/ng.3087},
  journal = {Nature Genetics},
  month = {aug},
  pages = {1126-1130},
  title = {Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.},
  url = {http://www.nature.com/articles/ng.3087.pdf},
  volume = {46},
  year = {2014}
}

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

Journal article published in 2014 by Em M. van Leeuwen, Lm M. van Koolwijk, Pt T. de Jong, Cm M. van Duijn, Pg G. Hysi, Cy-Y. Cheng

, Jessica N. Cooke Bailey, Henriët Springelkamp, Aw W. Hewitt, Tanja Zeller, Stuart Macgregor, René Höhn, Hysi Pg, Y. X. Wang, Gudmar Thorleifsson and other authors. Em M. van Leeuwen, Lm M. van Koolwijk, Pt T. de Jong, Cm M. van Duijn, Pg G. Hysi, Cy-Y. Cheng

, Jessica N. Cooke Bailey, Henriët Springelkamp, Aw W. Hewitt, Tanja Zeller, Stuart Macgregor, René Höhn, Hysi Pg, Y. X. Wang, Gudmar Thorleifsson, Yingfeng Zheng, Jn N. C. Bailey, Wd D. Ramdas, Liang Xu, Eranga Vithana, Robert Wojciechowski, Arni B. Stefansson, Cc-C. Khor, Cheng Cy, Jiemin Liao, Veronique Vitart, Najaf Amin, Jl L. Haines, Seyhan Yazar

, Abhishek Nag, Ayse B. Ozel, Ps S. Wild, Jz Z. Li, Bw W. Fleck, Se E. Staffieri, Yy-Y. Teo, Yx X. Wang, Gabriel Cuellar-Partida, Xiaoyan Luo, Rc C. W. Wolfs, Cristina Venturini

, Rr Rand Allingham, Tl L. Young, Je E. Richards, Alireza Mirshahi, Andrea Senft, Lc C. Karssen, Céline Bellenguez, Ai I. Iglesias, Jf F. Wilson, Jh H. Kang, Ty-Y. Wong, E. M. Van Leeuwen, Bailey Jnc, Vesteinn Jonsson, R. Rand Allingham, Unnur Thorsteinsdottir, Dominiek D. G. Despriet, Sarah Ennis, Se E. Moroi, Ng G. Martin, Nm M. Jansonius, Rene Hohn, Es-Shyong Tai, Philippe Amouyel

, James Kirwan, L. M. E. Van Koolwijk, Elisabeth M. van Leeuwen, Michael A. Hauser, Fridbert Jonasson, Paul Leo, Sj J. Loomis, Rhys Fogarty, Fernando Rivadeneira, Lisa Kearns, T.-Y. Wong, Kj J. Lackner, P. T. V. M. De Jong, Cl L. Simpson

, Ce E. Pennell, E. Shyong Tai, Ben A. Oostra, Ag G. Uitterlinden, J. J. Wang, Sm-M. Saw, E. Rochtchina, Aj J. Lotery

, J. Attia, Je E. Bailey-Wilson, R. Scott, Leonieke M. E. van Koolwijk, Albert Hofman, E. G. Holliday, Johannes R. Vingerling, P. N. Baird, Cécilia Maubaret, J. Xie, Norbert Pfeiffer, M. Inouye, Hg G. Lemij, X. Sim, M. H. Brilliant, Lr R. Pasquale

, D. L. Budenz, Hewitt Aw, Cécile Delcourt, W. G. Christen, Td D. Spector, J. Fingert, D. S. Friedman, Cc C. W. Klaver, D. Gaasterland, Ks S. Small, T. Gaasterland, J. H. Kang, Kp P. Burdon

, P. Kraft, Kari Stefansson, R. K. Lee, Paulus T. V. M. de Jong, P. A. Lichter, Y. Liu, Pericak-Vance, Ananth Viswanathan, A. Realini, J. S. Schuman, Da A. Mackey, W. K. Scott, Je E. Craig, K. Singh, Jl L. Wiggs, A. J. Sit, C. M. Van Duijn, D. Vollrath, Cj J. Hammond

, Weinreb, Tin Aung, G. Wollstein, D. J. Zack, K. Zhang, P. Donnelly, I. Barroso, J. M. Blackwell, E. Bramon, Brown, J. P. Casas, A. Corvin, P. Deloukas, M. Gillman, E. Gray, H. S. Markus, Bmes Gwas Group, C. G. Mathew, O. T. McCann, J. Liddle, S. C. Potter, Neighborhood Consortium, R. Ravindrarajah, Wellcome Trust Case Control Consortium 2., M. Ricketts, Ramdas Wd, M. Waller, N. W. Wood, C. C. A. Spencer, David Mackey Ao, G. Band, C. Freeman, G. Hellenthal, E. Giannoulatou, M. Pirinen, R. Pearson, A. Strange, Z. Su, D. Vukcevic

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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.

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

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