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32 results on '"Yonova-Doing, E"'

1. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, A, Malik, R., Hachiya, T., Jürgenson, T., Namba, S., Posner, D.C., Kamanu, F.K., Koido, M., Grand, Q. Le, Shi, M., He, Y., Georgakis, M.K., Caro, I., Krebs, K., Liaw, Y.C., Vaura, F.C., Lin, K., Winsvold, B.S., Srinivasasainagendra, V., Parodi, L., Bae, H.J., Chauhan, G., Chong, M.R., Tomppo, L., Akinyemi, R., Roshchupkin, G.V., Habib, N., Jee, Y.H., Thomassen, J.Q., Abedi, V., Cárcel-Márquez, J., Nygaard, M., Leonard, H.L., Yang, C., Yonova-Doing, E., Knol, M.J., Lewis, A.J., Judy, R.L., Ago, T., Amouyel, P., Armstrong, N.D., Bakker, M.K., Bartz, T.M., Bennett, D.A., Bis, J.C., Bordes, C., Børte, S., Cain, A., Ridker, P.M., Cho, K., Chen, Z., Cruchaga, C., Cole, J.W., Jager, P.L., Cid, R. de, Endres, M., Ferreira, L.E., Geerlings, M.I., Gasca, N.C., Gudnason, V., Hata, J., He, J., Heath, A.K., Ho, Y.L., Havulinna, A.S., Hopewell, J.C., Hyacinth, H.I., Inouye, M., Jacob, M.A., Jeon, C.E., Jern, C., Kamouchi, M., Keene, K.L., Kitazono, T., Kittner, S.J., Konuma, T., Kumar, A., Lacaze, P., Launer, L.J., Lee, K.J., Lepik, K., Li, J, Li, L, Manichaikul, A., Markus, H.S., Marston, N.A., Meitinger, T., Mitchell, B.D., Montellano, F.A., Morisaki, T., Mosley, T.H., Nalls, M.A., Nordestgaard, B.G., O'Donnell, M.J., Okada, Y., Onland-Moret, N.C., Ovbiagele, B., Peters, A., Psaty, B.M., Rich, S.S., Tuladhar, A.M., Leeuw, F.E. de, Dichgans, M., Debette, S., Mishra, A, Malik, R., Hachiya, T., Jürgenson, T., Namba, S., Posner, D.C., Kamanu, F.K., Koido, M., Grand, Q. Le, Shi, M., He, Y., Georgakis, M.K., Caro, I., Krebs, K., Liaw, Y.C., Vaura, F.C., Lin, K., Winsvold, B.S., Srinivasasainagendra, V., Parodi, L., Bae, H.J., Chauhan, G., Chong, M.R., Tomppo, L., Akinyemi, R., Roshchupkin, G.V., Habib, N., Jee, Y.H., Thomassen, J.Q., Abedi, V., Cárcel-Márquez, J., Nygaard, M., Leonard, H.L., Yang, C., Yonova-Doing, E., Knol, M.J., Lewis, A.J., Judy, R.L., Ago, T., Amouyel, P., Armstrong, N.D., Bakker, M.K., Bartz, T.M., Bennett, D.A., Bis, J.C., Bordes, C., Børte, S., Cain, A., Ridker, P.M., Cho, K., Chen, Z., Cruchaga, C., Cole, J.W., Jager, P.L., Cid, R. de, Endres, M., Ferreira, L.E., Geerlings, M.I., Gasca, N.C., Gudnason, V., Hata, J., He, J., Heath, A.K., Ho, Y.L., Havulinna, A.S., Hopewell, J.C., Hyacinth, H.I., Inouye, M., Jacob, M.A., Jeon, C.E., Jern, C., Kamouchi, M., Keene, K.L., Kitazono, T., Kittner, S.J., Konuma, T., Kumar, A., Lacaze, P., Launer, L.J., Lee, K.J., Lepik, K., Li, J, Li, L, Manichaikul, A., Markus, H.S., Marston, N.A., Meitinger, T., Mitchell, B.D., Montellano, F.A., Morisaki, T., Mosley, T.H., Nalls, M.A., Nordestgaard, B.G., O'Donnell, M.J., Okada, Y., Onland-Moret, N.C., Ovbiagele, B., Peters, A., Psaty, B.M., Rich, S.S., Tuladhar, A.M., Leeuw, F.E. de, Dichgans, M., and Debette, S.
Abstract: Item does not contain fulltext, Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Published: 2022

2. Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, and Debette, S
Published: 2022

3. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries (Nature, (2022), 611, 7934, (115-123), 10.1038/s41586-022-05165-3)

Author: Mishra, A, Malik, R, Hachiya, T, Jürgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, YC, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, HJ, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Cárcel-Márquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Børte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, YL, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, KJ, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O’Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Mishra, A, Malik, R, Hachiya, T, Jürgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, YC, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, HJ, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Cárcel-Márquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Børte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, YL, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, KJ, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O’Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, and Rich, SS
Abstract: In the version of this article initially published, the name of the PRECISE4Q Consortium was misspelled as “PRECISEQ” and has now been amended in the HTML and PDF versions of the article. Further, data in the first column of Supplementary Table 55 were mistakenly shifted and have been corrected in the file accompanying the HTML version of the article.
Published: 2022

4. Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, AV, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Velez Edwards, DR, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, De Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, I, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, YV, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, AI, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Davey Smith, G, Boer, RAD, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, MI, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, Van der Harst, P, Van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, DI, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, and United Kingdom Research and Innovation
Subjects: Genetics & Heredity, Understanding Society Scientific Group, Science & Technology, business.industry, Published Erratum, Million Veteran Program, MEDLINE, Computational biology, 06 Biological Sciences, Biology, Blood pressure, Text mining, Meta-analysis, EPIC-InterAct, Genetics, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business, Life Sciences & Biomedicine, EPIC-CVD, 11 Medical and Health Sciences, LifeLines Cohort Study, Developmental Biology
Abstract: In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article.
Published: 2021
Full Text: View/download PDF

5. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P., Feofanova, E. V., Lahrouchi, N., Ntalla, I., Karthikeyan, S., Cook, J., Chen, L., Mifsud, B., Yao, C., Kraja, A. T., Cartwright, J. H., Hellwege, J. N., Giri, A., Tragante, V., Thorleifsson, G., Liu, D. J., Prins, B. P., Stewart, I. D., Cabrera, C. P., Eales, J. M., Akbarov, A., Auer, P. L., Bielak, L. F., Bis, J. C., Braithwaite, V. S., Brody, J. A., Daw, E. W., Warren, H. R., Drenos, F., Nielsen, S. F., Faul, J. D., Fauman, E. B., Fava, C., Ferreira, T., Foley, C. N., Franceschini, N., Gao, H., Giannakopoulou, O., Giulianini, F., Gudbjartsson, D. F., Guo, X., Harris, S. E., Havulinna, A. S., Helgadottir, A., Huffman, J. E., Hwang, S. -J., Kanoni, S., Kontto, J., Larson, M. G., Li-Gao, R., Lindstrom, J., Lotta, L. A., Lu, Y., Luan, J., Mahajan, A., Malerba, G., Masca, N. G. D., Mei, H., Menni, C., Mook-Kanamori, D. O., Mosen-Ansorena, D., Muller-Nurasyid, M., Pare, G., Paul, D. S., Perola, M., Poveda, A., Rauramaa, R., Richard, M., Richardson, T. G., Sepulveda, N., Sim, X., Smith, A. V., Smith, J. A., Staley, J. R., Stanakova, A., Sulem, P., Theriault, S., Thorsteinsdottir, U., Trompet, S., Varga, T. V., Velez Edwards, D. R., Veronesi, G., Weiss, S., Willems, S. M., Yao, J., Young, R., Yu, B., Zhang, W., Zhao, J. -H., Zhao, W., Evangelou, E., Aeschbacher, S., Asllanaj, E., Blankenberg, S., Bonnycastle, L. L., Bork-Jensen, J., Brandslund, I., Braund, P. S., Burgess, S., Cho, K., Christensen, C., Connell, J., Mutsert, R., Dominiczak, A. F., Dorr, M., Eiriksdottir, G., Farmaki, A. -E., Gaziano, J. M., Grarup, N., Grove, M. L., Hallmans, G., Hansen, T., Have, C. T., Heiss, G., Jorgensen, M. E., Jousilahti, P., Kajantie, E., Kamat, M., Karajamaki, A. M., Karpe, F., Koistinen, H. A., Kovesdy, C. P., Kuulasmaa, K., Laatikainen, T., Lannfelt, L., Lee, I. -T., Lee, W. -J., de Boer, R. A., van der Harst, P., van der Meer, P., Verweij, N., Linneberg, A., Martin, L. W., Moitry, M., Nadkarni, G., Neville, M. J., Palmer, C. N. A., Papanicolaou, G. J., Pedersen, O., Peters, J., Poulter, N., Rasheed, A., Rasmussen, K. L., Rayner, N. W., Magi, R., Renstrom, F., Rettig, R., Rossouw, J., Schreiner, P. J., Sever, P. S., Sigurdsson, E. L., Skaaby, T., Sun, Y. V., Sundstrom, J., Thorgeirsson, G., Esko, T., Trabetti, E., Tsao, P. S., Tuomi, T., Turner, S. T., Tzoulaki, I., Vaartjes, I., Vergnaud, A. -C., Willer, C. J., Wilson, P. W. F., Witte, D. R., Yonova-Doing, E., Zhang, H., Aliya, N., Almgren, P., Amouyel, P., Asselbergs, F. W., Barnes, M. R., Blakemore, A. I., Boehnke, M., Bots, M. L., Bottinger, E. P., Buring, J. E., Chambers, J. C., Chen, Y. -D. I., Chowdhury, R., Conen, D., Correa, A., Davey Smith, G., Boer, R. A., Deary, I. J., Dedoussis, G., Deloukas, P., Di Angelantonio, E., Elliott, P., Butterworth, A. S., Danesh, J., Langenberg, C., Mccarthy, M. I., Franks, P. W., Rolandsson, O., Wareham, N. J., Felix, S. B., Ferrieres, J., Ford, I., Fornage, M., Franks, S., Frossard, P., Gambaro, G., Gaunt, T. R., Groop, L., Gudnason, V., Harris, T. B., Hayward, C., Hennig, B. J., Herzig, K. -H., Ingelsson, E., Tuomilehto, J., Jarvelin, M. -R., Jukema, J. W., Kardia, S. L. R., Kee, F., Kooner, J. S., Kooperberg, C., Launer, L. J., Lind, L., Loos, R. J. F., Majumder, A. S., Laakso, M., Melander, O., Mohlke, K. L., Murray, A. D., Nordestgaard, B. G., Orho-Melander, M., Packard, C. J., Padmanabhan, S., Palmas, W., Polasek, O., Porteous, D. J., Prentice, A. M., Province, M. A., Relton, C. L., Rice, K., Ridker, P. M., Rosendaal, F. R., Rotter, J. I., Rudan, I., Salomaa, V., Samani, N. J., Sattar, N., Sheu, W. H. -H., Smith, B. H., Soranzo, N., Spector, T. D., Starr, J. M., Sebert, S., Taylor, K. D., Lakka, T. A., Timpson, N. J., Tobin, M. D., Zeggini, E., Ramachandran, V. S., Virtamo, J., Volker, U., Weir, D. R., Charchar, F. J., Edwards, D. R. V., Edwards, T. L., Hung, A. M., O'Donnell, C. J., Tomaszewski, M., Caulfield, M. J., Holm, H., Lindgren, C. M., Liu, C., Manning, A. K., Morris, A. P., Morrison, A. C., Psaty, B. M., Saleheen, D., Stefansson, K., Boerwinkle, E., Chasman, D. I., Levy, D., Newton-Cheh, C., Munroe, P. B., Howson, J. M. M., Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), UNIVERSITY OF OULU, Epidemiology, Complex Disease Genetics, Research Programs Unit, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, HUS Children and Adolescents, Lastentautien yksikkö, Clinicum, Children's Hospital, Helsinki University Hospital Area, HUS Internal Medicine and Rehabilitation, Department of Medicine, Department of Biochemistry and Developmental Biology, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Endokrinologian yksikkö, Department of Public Health, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Feofanova, Elena V [0000-0003-1428-7199], Chasman, Daniel I [0000-0003-3357-0862], Munroe, Patricia B [0000-0002-4176-2947], Howson, Joanna MM [0000-0001-7618-0050], Apollo - University of Cambridge Repository, Cardiology, and ACS - Heart failure & arrhythmias
Subjects: Candidate gene, Blood Pressure, GATA5 Transcription Factor, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Hypertension, Mutation, Phospholipase C beta, Polymorphism, Single Nucleotide, LOCI, Genome-wide association study, 0302 clinical medicine, Polymorphism (computer science), genetics, GENOME-WIDE ASSOCIATION, MENDELIAN RANDOMIZATION, COMMON VARIANTS, IDENTIFIES COMMON, RISK, FREQUENCY, TRAITS, HYPERTENSION, GENETICS, EPIC-CVD, 11 Medical and Health Sciences, health care economics and organizations, Genetics & Heredity, Genetics, 0303 health sciences, Million Veteran Program, 1184 Genetics, developmental biology, physiology, Single Nucleotide, humanities, 3. Good health, genetic association study, EPIC-InterAct, epidemiology, Life Sciences & Biomedicine, Understanding Society Scientific Group, hypertension, education, Biology, Article, 03 medical and health sciences, Mendelian randomization, Polymorphism, Allele frequency, Gene, 030304 developmental biology, Science & Technology, 06 Biological Sciences, meta-analysis, Minor allele frequency, genome-wide association studies, 3111 Biomedicine, 030217 neurology & neurosurgery, LifeLines Cohort Study, Developmental Biology
Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P
Published: 2020
Full Text: View/download PDF

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

Author: Yonova-Doing, E. (Ekaterina), Zhao, W. (Wanting), Igo Jr., R.P. (Robert), Wang, C. (Chunliang), Sundaresan, P. (Periasamy), Lee, K.E. (Kristine), Jun, G.R. (Gyungah R.), Alves, A.C. (Alexessander Couto), Chai, X. (Xiaoran), Chan, A.S.Y. (Anita S. Y.), Lee, M.C. (Mei Chin), Fong, A. (Allan), Tan, A.G. (Ava G.), Khor, C.C., Chew, E.Y. (Emily Y.), Hysi, P.G. (Pirro G.), Fan, Q. (Qiao), Chua, J. (Jacqueline), Chung, J. (Jaeyoon), Liao, J. (Jiemin), Colijn, J.M. (Johanna), Burdon, K.P. (Kathryn P.), Fritsche, L.G. (Lars), Swift, M.K. (Maria K.), Hilmy, M.H. (Maryam H.), Chee, M.L. (Miao Ling), Tedja, M. (Milly), Bonnemaijer, P.W.M. (Pieter), Gupta, P. (Preeti), Tan, Q.S. (Queenie S.), Li, Z. (Zheng), Vithana, E.N. (Eranga), Ravindran, R.D. (Ravilla D.), Chee, S.-P. (Soon-Phaik), Shi, Y. (Yuan), Liu, W. (Wenting), Su, X. (Xinyi), Sim, X. (Xueling), Shen, Y. (Yang), Wang, Y.X. (Ya Xing), Li, H. (Hengtong), Tham, Y.-C. (Yih-Chung), Teo, Y.Y. (Yik Ying), Aung, T. (Tin), Small, K.S. (Kerrin S.), Mitchell, P. (Paul), Jonas, J.B. (Jost B.), Wong, T.Y. (Tien Yin), Fletcher, A. (Astrid), Klaver, C.C.W. (Caroline), Klein, B.E.K. (Barbara E. K.), Wang, J.J. (Jie Jin), Iyengar, S.K. (Sudha K.), Hammond, C.J. (Christopher J.), Cheng, C.-Y. (Ching-Yu), Yonova-Doing, E. (Ekaterina), Zhao, W. (Wanting), Igo Jr., R.P. (Robert), Wang, C. (Chunliang), Sundaresan, P. (Periasamy), Lee, K.E. (Kristine), Jun, G.R. (Gyungah R.), Alves, A.C. (Alexessander Couto), Chai, X. (Xiaoran), Chan, A.S.Y. (Anita S. Y.), Lee, M.C. (Mei Chin), Fong, A. (Allan), Tan, A.G. (Ava G.), Khor, C.C., Chew, E.Y. (Emily Y.), Hysi, P.G. (Pirro G.), Fan, Q. (Qiao), Chua, J. (Jacqueline), Chung, J. (Jaeyoon), Liao, J. (Jiemin), Colijn, J.M. (Johanna), Burdon, K.P. (Kathryn P.), Fritsche, L.G. (Lars), Swift, M.K. (Maria K.), Hilmy, M.H. (Maryam H.), Chee, M.L. (Miao Ling), Tedja, M. (Milly), Bonnemaijer, P.W.M. (Pieter), Gupta, P. (Preeti), Tan, Q.S. (Queenie S.), Li, Z. (Zheng), Vithana, E.N. (Eranga), Ravindran, R.D. (Ravilla D.), Chee, S.-P. (Soon-Phaik), Shi, Y. (Yuan), Liu, W. (Wenting), Su, X. (Xinyi), Sim, X. (Xueling), Shen, Y. (Yang), Wang, Y.X. (Ya Xing), Li, H. (Hengtong), Tham, Y.-C. (Yih-Chung), Teo, Y.Y. (Yik Ying), Aung, T. (Tin), Small, K.S. (Kerrin S.), Mitchell, P. (Paul), Jonas, J.B. (Jost B.), Wong, T.Y. (Tien Yin), Fletcher, A. (Astrid), Klaver, C.C.W. (Caroline), Klein, B.E.K. (Barbara E. K.), Wang, J.J. (Jie Jin), Iyengar, S.K. (Sudha K.), Hammond, C.J. (Christopher J.), and Cheng, C.-Y. (Ching-Yu)
Abstract: Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10
Published: 2020
Full Text: View/download PDF

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

Author: Yonova-Doing, E., Zhao, W., Igo, R.P., Jr., Wang, Chaolong, Sundaresan, Periasamy, Lee, Kristine E., Klaver, C.C.W., Hammond, C.J., Cheng, C.Y., Yonova-Doing, E., Zhao, W., Igo, R.P., Jr., Wang, Chaolong, Sundaresan, Periasamy, Lee, Kristine E., Klaver, C.C.W., Hammond, C.J., and Cheng, C.Y.
Abstract: Contains fulltext : 228408.pdf (publisher's version ) (Open Access)
Published: 2020

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

Author: Yonova-Doing, E, Zhao, W, Igo, RP, Wang, C, Sundaresan, P, Lee, KE, Jun, GR, Alves, AC, Chai, X, Chan, ASY, Lee, MC, Fong, A, Tan, AG, Khor, CC, Chew, EY, Hysi, PG, Fan, Q, Chua, J, Chung, J, Liao, J, Colijn, JM, Burdon, KP, Fritsche, LG, Swift, MK, Hilmy, MH, Chee, ML, Tedja, M, Bonnemaijer, PWM, Gupta, P, Tan, QS, Li, Z, Vithana, EN, Ravindran, RD, Chee, S-P, Shi, Y, Liu, W, Su, X, Sim, X, Shen, Y, Wang, YX, Li, H, Tham, Y-C, Teo, YY, Aung, T, Small, KS, Mitchell, P, Jonas, JB, Wong, TY, Fletcher, AE, Klaver, CCW, Klein, BEK, Wang, JJ, Iyengar, SK, Hammond, CJ, Cheng, C-Y, Yonova-Doing, E, Zhao, W, Igo, RP, Wang, C, Sundaresan, P, Lee, KE, Jun, GR, Alves, AC, Chai, X, Chan, ASY, Lee, MC, Fong, A, Tan, AG, Khor, CC, Chew, EY, Hysi, PG, Fan, Q, Chua, J, Chung, J, Liao, J, Colijn, JM, Burdon, KP, Fritsche, LG, Swift, MK, Hilmy, MH, Chee, ML, Tedja, M, Bonnemaijer, PWM, Gupta, P, Tan, QS, Li, Z, Vithana, EN, Ravindran, RD, Chee, S-P, Shi, Y, Liu, W, Su, X, Sim, X, Shen, Y, Wang, YX, Li, H, Tham, Y-C, Teo, YY, Aung, T, Small, KS, Mitchell, P, Jonas, JB, Wong, TY, Fletcher, AE, Klaver, CCW, Klein, BEK, Wang, JJ, Iyengar, SK, Hammond, CJ, and Cheng, C-Y
Abstract: Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10-16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10-19), TMPRSS5 (rs4936279, P = 2.5 × 10-10), LINC01412 (rs16823886, P = 1.3 × 10-9), GLTSCR1 (rs1005911, P = 9.8 × 10-9), and COMMD1 (rs62149908, P = 1.2 × 10-8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.
Published: 2020

9. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P, Feofanova, E, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, A, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Edwards, DRV, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, de Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, T, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, Y, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, A, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Smith, GD, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, M, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, J, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, van der Harst, P, van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, D, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, Surendran, P, Feofanova, E, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, A, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Edwards, DRV, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, de Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, T, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, Y, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, A, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Smith, GD, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, M, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, J, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, van der Harst, P, van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, D, Levy, D, Newton-Cheh, C, Munroe, PB, and Howson, JMM
Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
Published: 2020

10. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Howson, J. M. (Joanna M. M.), Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), and Howson, J. M. (Joanna M. M.)
Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 x 10(⁻⁸)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets., Correction A Publisher Correction to this article was published on 16 March 2021.
Published: 2020

11. Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke

Author: Abraham, G, Malik, R, Yonova-Doing, E, Salim, A, Wang, T, Danesh, J, Butterworth, AS, Howson, JMM, Inouye, M, Dichgans, M, Abraham, G, Malik, R, Yonova-Doing, E, Salim, A, Wang, T, Danesh, J, Butterworth, AS, Howson, JMM, Inouye, M, and Dichgans, M
Abstract: Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.
Published: 2019

12. 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
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13. 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

14. 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

15. 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

16. 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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17. 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

18. 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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19. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries.

Author: Mishra A, Malik R, Hachiya T, Jürgenson T, Namba S, Posner DC, Kamanu FK, Koido M, Le Grand Q, Shi M, He Y, Georgakis MK, Caro I, Krebs K, Liaw YC, Vaura FC, Lin K, Winsvold BS, Srinivasasainagendra V, Parodi L, Bae HJ, Chauhan G, Chong MR, Tomppo L, Akinyemi R, Roshchupkin GV, Habib N, Jee YH, Thomassen JQ, Abedi V, Cárcel-Márquez J, Nygaard M, Leonard HL, Yang C, Yonova-Doing E, Knol MJ, Lewis AJ, Judy RL, Ago T, Amouyel P, Armstrong ND, Bakker MK, Bartz TM, Bennett DA, Bis JC, Bordes C, Børte S, Cain A, Ridker PM, Cho K, Chen Z, Cruchaga C, Cole JW, de Jager PL, de Cid R, Endres M, Ferreira LE, Geerlings MI, Gasca NC, Gudnason V, Hata J, He J, Heath AK, Ho YL, Havulinna AS, Hopewell JC, Hyacinth HI, Inouye M, Jacob MA, Jeon CE, Jern C, Kamouchi M, Keene KL, Kitazono T, Kittner SJ, Konuma T, Kumar A, Lacaze P, Launer LJ, Lee KJ, Lepik K, Li J, Li L, Manichaikul A, Markus HS, Marston NA, Meitinger T, Mitchell BD, Montellano FA, Morisaki T, Mosley TH, Nalls MA, Nordestgaard BG, O'Donnell MJ, Okada Y, Onland-Moret NC, Ovbiagele B, Peters A, Psaty BM, Rich SS, Rosand J, Sabatine MS, Sacco RL, Saleheen D, Sandset EC, Salomaa V, Sargurupremraj M, Sasaki M, Satizabal CL, Schmidt CO, Shimizu A, Smith NL, Sloane KL, Sutoh Y, Sun YV, Tanno K, Tiedt S, Tatlisumak T, Torres-Aguila NP, Tiwari HK, Trégouët DA, Trompet S, Tuladhar AM, Tybjærg-Hansen A, van Vugt M, Vibo R, Verma SS, Wiggins KL, Wennberg P, Woo D, Wilson PWF, Xu H, Yang Q, Yoon K, Millwood IY, Gieger C, Ninomiya T, Grabe HJ, Jukema JW, Rissanen IL, Strbian D, Kim YJ, Chen PH, Mayerhofer E, Howson JMM, Irvin MR, Adams H, Wassertheil-Smoller S, Christensen K, Ikram MA, Rundek T, Worrall BB, Lathrop GM, Riaz M, Simonsick EM, Kõrv J, França PHC, Zand R, Prasad K, Frikke-Schmidt R, de Leeuw FE, Liman T, Haeusler KG, Ruigrok YM, Heuschmann PU, Longstreth WT, Jung KJ, Bastarache L, Paré G, Damrauer SM, Chasman DI, Rotter JI, Anderson CD, Zwart JA, Niiranen TJ, Fornage M, Liaw YP, Seshadri S, Fernández-Cadenas I, Walters RG, Ruff CT, Owolabi MO, Huffman JE, Milani L, Kamatani Y, Dichgans M, and Debette S
Published: 2022
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20. Stroke genetics informs drug discovery and risk prediction across ancestries.

Author: Mishra A, Malik R, Hachiya T, Jürgenson T, Namba S, Posner DC, Kamanu FK, Koido M, Le Grand Q, Shi M, He Y, Georgakis MK, Caro I, Krebs K, Liaw YC, Vaura FC, Lin K, Winsvold BS, Srinivasasainagendra V, Parodi L, Bae HJ, Chauhan G, Chong MR, Tomppo L, Akinyemi R, Roshchupkin GV, Habib N, Jee YH, Thomassen JQ, Abedi V, Cárcel-Márquez J, Nygaard M, Leonard HL, Yang C, Yonova-Doing E, Knol MJ, Lewis AJ, Judy RL, Ago T, Amouyel P, Armstrong ND, Bakker MK, Bartz TM, Bennett DA, Bis JC, Bordes C, Børte S, Cain A, Ridker PM, Cho K, Chen Z, Cruchaga C, Cole JW, de Jager PL, de Cid R, Endres M, Ferreira LE, Geerlings MI, Gasca NC, Gudnason V, Hata J, He J, Heath AK, Ho YL, Havulinna AS, Hopewell JC, Hyacinth HI, Inouye M, Jacob MA, Jeon CE, Jern C, Kamouchi M, Keene KL, Kitazono T, Kittner SJ, Konuma T, Kumar A, Lacaze P, Launer LJ, Lee KJ, Lepik K, Li J, Li L, Manichaikul A, Markus HS, Marston NA, Meitinger T, Mitchell BD, Montellano FA, Morisaki T, Mosley TH, Nalls MA, Nordestgaard BG, O'Donnell MJ, Okada Y, Onland-Moret NC, Ovbiagele B, Peters A, Psaty BM, Rich SS, Rosand J, Sabatine MS, Sacco RL, Saleheen D, Sandset EC, Salomaa V, Sargurupremraj M, Sasaki M, Satizabal CL, Schmidt CO, Shimizu A, Smith NL, Sloane KL, Sutoh Y, Sun YV, Tanno K, Tiedt S, Tatlisumak T, Torres-Aguila NP, Tiwari HK, Trégouët DA, Trompet S, Tuladhar AM, Tybjærg-Hansen A, van Vugt M, Vibo R, Verma SS, Wiggins KL, Wennberg P, Woo D, Wilson PWF, Xu H, Yang Q, Yoon K, Millwood IY, Gieger C, Ninomiya T, Grabe HJ, Jukema JW, Rissanen IL, Strbian D, Kim YJ, Chen PH, Mayerhofer E, Howson JMM, Irvin MR, Adams H, Wassertheil-Smoller S, Christensen K, Ikram MA, Rundek T, Worrall BB, Lathrop GM, Riaz M, Simonsick EM, Kõrv J, França PHC, Zand R, Prasad K, Frikke-Schmidt R, de Leeuw FE, Liman T, Haeusler KG, Ruigrok YM, Heuschmann PU, Longstreth WT, Jung KJ, Bastarache L, Paré G, Damrauer SM, Chasman DI, Rotter JI, Anderson CD, Zwart JA, Niiranen TJ, Fornage M, Liaw YP, Seshadri S, Fernández-Cadenas I, Walters RG, Ruff CT, Owolabi MO, Huffman JE, Milani L, Kamatani Y, Dichgans M, and Debette S
Subjects: Humans, Brain Ischemia genetics, Genome-Wide Association Study, Molecular Targeted Therapy, Multifactorial Inheritance, Europe ethnology, Asia, Eastern ethnology, Africa ethnology, Drug Discovery, Genetic Predisposition to Disease genetics, Ischemic Stroke genetics
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries., (© 2022. The Author(s).)
Published: 2022
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21. Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.

Author: Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, and Howson JMM
Subjects: Blood Proteins genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Proteome genetics, Risk Factors, Atrial Fibrillation genetics, Diabetes Mellitus, Type 2 genetics, Stroke genetics
Abstract: Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10 -4 ). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke., (© 2022. The Author(s).)
Published: 2022
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22. Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion.

Author: Veprik A, Denwood G, Liu D, Bany Bakar R, Morfin V, McHugh K, Tebeka NN, Vetterli L, Yonova-Doing E, Gribble F, Reimann F, Hoehn KL, Hemsley PA, Ahnfelt-Rønne J, Rorsman P, Zhang Q, de Wet H, and Cantley J
Subjects: Acetyl Coenzyme A metabolism, Acetyl-CoA Carboxylase metabolism, Animals, Glucagon, Glucose metabolism, Mice, Glucagon-Secreting Cells metabolism, Insulin-Secreting Cells metabolism
Abstract: Dysregulated glucagon secretion from pancreatic alpha-cells is a key feature of type-1 and type-2 diabetes (T1D and T2D), yet our mechanistic understanding of alpha-cell function is underdeveloped relative to insulin-secreting beta-cells. Here we show that the enzyme acetyl-CoA-carboxylase 1 (ACC1), which couples glucose metabolism to lipogenesis, plays a key role in the regulation of glucagon secretion. Pharmacological inhibition of ACC1 in mouse islets or αTC9 cells impaired glucagon secretion at low glucose (1 mmol/l). Likewise, deletion of ACC1 in alpha-cells in mice reduced glucagon secretion at low glucose in isolated islets, and in response to fasting or insulin-induced hypoglycaemia in vivo. Electrophysiological recordings identified impaired K ATP channel activity and P/Q- and L-type calcium currents in alpha-cells lacking ACC1, explaining the loss of glucose-sensing. ACC-dependent alterations in S-acylation of the K ATP channel subunit, Kir6.2, were identified by acyl-biotin exchange assays. Histological analysis identified that loss of ACC1 caused a reduction in alpha-cell area of the pancreas, glucagon content and individual alpha-cell size, further impairing secretory capacity. Loss of ACC1 also reduced the release of glucagon-like peptide 1 (GLP-1) in primary gastrointestinal crypts. Together, these data reveal a role for the ACC1-coupled pathway in proglucagon-expressing nutrient-responsive endocrine cell function and systemic glucose homeostasis., (© 2022. The Author(s).)
Published: 2022
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23. Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.

Author: Cai N, Gomez-Duran A, Yonova-Doing E, Kundu K, Burgess AI, Golder ZJ, Calabrese C, Bonder MJ, Camacho M, Lawson RA, Li L, Williams-Gray CH, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Stewart ID, Pietzner M, Wareham NJ, Langenberg C, Danesh J, Walter K, Rothwell PM, Howson JMM, Stegle O, Chinnery PF, and Soranzo N
Subjects: Age of Onset, Blood Donors, Cardiovascular Diseases blood, Cardiovascular Diseases epidemiology, DNA, Mitochondrial blood, Female, Follow-Up Studies, Haplotypes genetics, Humans, Male, Middle Aged, Mitochondria pathology, N-Formylmethionine metabolism, Proteostasis, Risk Factors, United Kingdom epidemiology, Biomarkers blood, Cardiovascular Diseases genetics, DNA, Mitochondrial genetics, Mitochondria genetics
Abstract: Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N-formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2021
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24. Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Author: Yonova-Doing E, Zhao W, Igo RP Jr, Wang C, Sundaresan P, Lee KE, Jun GR, Alves AC, Chai X, Chan ASY, Lee MC, Fong A, Tan AG, Khor CC, Chew EY, Hysi PG, Fan Q, Chua J, Chung J, Liao J, Colijn JM, Burdon KP, Fritsche LG, Swift MK, Hilmy MH, Chee ML, Tedja M, Bonnemaijer PWM, Gupta P, Tan QS, Li Z, Vithana EN, Ravindran RD, Chee SP, Shi Y, Liu W, Su X, Sim X, Shen Y, Wang YX, Li H, Tham YC, Teo YY, Aung T, Small KS, Mitchell P, Jonas JB, Wong TY, Fletcher AE, Klaver CCW, Klein BEK, Wang JJ, Iyengar SK, Hammond CJ, and Cheng CY
Subjects: Alleles, Cataract diagnosis, Genetic Association Studies, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Cataract etiology, Genetic Predisposition to Disease, Genetic Variation, SOXB1 Transcription Factors genetics
Abstract: Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h 2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10 -16 ) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10 -19 ), TMPRSS5 (rs4936279, P = 2.5 × 10 -10 ), LINC01412 (rs16823886, P = 1.3 × 10 -9 ), GLTSCR1 (rs1005911, P = 9.8 × 10 -9 ), and COMMD1 (rs62149908, P = 1.2 × 10 -8 ). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.
Published: 2020
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25. Author Correction: Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.

Author: Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, and Dichgans M
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2020
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26. Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.

Author: Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, and Dichgans M
Subjects: Aged, Blood Pressure, Body Mass Index, Brain Ischemia genetics, Comorbidity, Datasets as Topic, Female, Genome-Wide Association Study, Humans, Male, Medical History Taking, Middle Aged, Polymorphism, Single Nucleotide, Predictive Value of Tests, Risk Assessment methods, Smoking epidemiology, United Kingdom epidemiology, Brain Ischemia epidemiology, Genetic Predisposition to Disease, Genomics methods
Abstract: Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.
Published: 2019
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27. Phenotypic and genotypic correlation between myopia and intelligence.

Author: Williams KM, Hysi PG, Yonova-Doing E, Mahroo OA, Snieder H, and Hammond CJ
Subjects: Adolescent, Female, Genome, Human, Humans, Linear Models, Male, Multifactorial Inheritance genetics, Refractive Errors, Risk Factors, Twins genetics, Genetic Association Studies, Intelligence genetics, Myopia genetics
Abstract: Myopia, or near-sightedness, is our most common eye condition and the prevalence is increasing globally. Visual impairment will occur if uncorrected, whilst high myopia causes sight-threatening complications. Myopia is associated with higher intelligence. As both are heritable, we set out to examine whether there is a genetic correlation between myopia and intelligence in over 1,500 subjects (aged 14-18 years) from a twin birth cohort. The phenotypic correlation between refractive error and intelligence was -0.116 (p < 0.01) - the inverse correlation due to the fact that myopia is a negative refractive error. Bivariate twin modeling confirmed both traits were heritable (refractive error 85%, intelligence 47%) and the genetic correlation was -0.143 (95% CI -0.013 to -0.273). Of the small phenotypic correlation the majority (78%) was explained by genetic factors. Polygenic risk scores were constructed based on common genetic variants identified in previous genome-wide association studies of refractive error and intelligence. Genetic variants for intelligence and refractive error explain some of the reciprocal variance, suggesting genetic pleiotropy; in the best-fit model the polygenic score for intelligence explained 0.99% (p = 0.008) of refractive error variance. These novel findings indicate shared genetic factors contribute significantly to the covariance between myopia and intelligence.
Published: 2017
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28. 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 AI, Mishra A, Höhn R, Wojciechowski R, Khawaja AP, Nag A, Wang YX, Wang JJ, Cuellar-Partida G, Gibson J, Bailey JN, Vithana EN, Gharahkhani P, Boutin T, Ramdas WD, Zeller T, Luben RN, Yonova-Doing E, Viswanathan AC, Yazar S, Cree AJ, Haines JL, Koh JY, Souzeau E, Wilson JF, Amin N, Müller C, Venturini C, Kearns LS, Kang JH, Tham YC, Zhou T, van Leeuwen EM, Nickels S, Sanfilippo P, Liao J, van der Linde H, Zhao W, van Koolwijk LM, Zheng L, Rivadeneira F, Baskaran M, van der Lee SJ, Perera S, de Jong PT, Oostra BA, Uitterlinden AG, Fan Q, Hofman A, Tai ES, Vingerling JR, Sim X, Wolfs RC, Teo YY, Lemij HG, Khor CC, Willemsen R, Lackner KJ, Aung T, Jansonius NM, Montgomery G, Wild PS, Young TL, Burdon KP, Hysi PG, Pasquale LR, Wong TY, Klaver CC, Hewitt AW, Jonas JB, Mitchell P, Lotery AJ, Foster PJ, Vitart V, Pfeiffer N, Craig JE, Mackey DA, Hammond CJ, Wiggs JL, Cheng CY, van Duijn CM, and MacGregor S
Subjects: Female, Genome, Human, Genome-Wide Association Study, Glaucoma, Open-Angle pathology, Humans, Intraocular Pressure genetics, Male, Middle Aged, Optic Disk pathology, Optic Nerve Diseases pathology, Tonometry, Ocular, Cyclin-Dependent Kinase Inhibitor p21 genetics, Glaucoma, Open-Angle genetics, Homeodomain Proteins genetics, Optic Nerve Diseases genetics, Zebrafish Proteins genetics
Abstract: 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., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2017
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29. Do twins share the same dress code? Quantifying relative genetic and environmental contributions to subjective perceptions of "the dress" in a classical twin study.

Author: Mahroo OA, Williams KM, Hossain IT, Yonova-Doing E, Kozareva D, Yusuf A, Sheriff I, Oomerjee M, Soorma T, and Hammond CJ
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Male, Middle Aged, Registries, United Kingdom, White People, Clothing, Color Perception genetics, Gene-Environment Interaction, Twins, Dizygotic genetics, Twins, Monozygotic genetics
Abstract: The phenomenon of contrasting color perceptions of "the dress" photograph has gained scientific interest. The mechanism underlying why individuals differ is yet to be fully explained. We use the powerful twin model design to ascertain the relative contribution of genetic and environmental factors on perception variation. A sample of 466 twins from the British TwinsUK registry were invited to report what color they saw in a standard image of the dress in standard illumination. The mean age of the participants was 49.5 (SD = 17.8) years, and 85% were female. When asked to choose between white and gold (WG) or blue and black (BB), 328 reported WG (70.4%) and 135 (29.0%) reported BB. Subjects choosing WG were significantly older (p < 0.01), but there was no significant difference in gender. Monozygotic (MZ) twins were more concordant in their responses than dizygotic (DZ) twins (0.46 vs. 0.36). Twin modeling revealed that genetic factors accounted for 34% (95% confidence interval, 5%-59%) of variation in the reported color of the dress when adjusted for age, whereas environmental factors contributed 66% (95% CI, 41%-95%). This study suggests environmental factors play a significant role in how an individual perceives the color of "the dress."
Published: 2017
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30. The correlation between cognitive performance and retinal nerve fibre layer thickness is largely explained by genetic factors.

Author: Jones-Odeh E, Yonova-Doing E, Bloch E, Williams KM, Steves CJ, and Hammond CJ
Abstract: Retinal nerve fibre layer (RNFL) thickness has been associated with cognitive function but it is unclear whether RNFL thinning is secondary to cortical loss, or if the same disease process affects both. We explored whether there is phenotypic sharing between RNFL thickness and cognitive traits, and whether such sharing is due to genetic factors. Detailed eye and cognitive examination were performed on 1602 twins (mean age: 56.4 years; range: 18-89) from the TwinsUK cohort. Associations between RNFL thickness and ophthalmic, cognitive and other predictors were assessed using linear regression or analysis of variance models. Heritability analyses were performed using uni- and bivariate Cholesky decomposition models. RNFL was thinner with increase in myopia and with decrease in disc area (p < 0.001). A thicker RNFL was associated with better performance on mini mental state examination (MMSE, F(5,883) = 5.8, p < 0.001), and with faster reaction time (RT, β = -0.01; p = 0.01); independent of the effects of age, refractive error and disc area (p < 0.05). RNFL thickness was highly heritable (82%) but there was low phenotypic sharing between RNFL thickness and MMSE (5%, 95% CI: 0-10%) or RT (7%, 95% CI: 1-12%). This sharing, however, was mostly due to additive genetic effects (67% and 92% of the shared variance respectively).
Published: 2016
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31. 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 VJ, Ikram MK, Höhn R, Vitart V, Hewitt AW, Oexle K, Mäkelä KM, MacGregor S, Pirastu M, Fan Q, Cheng CY, St Pourcain B, McMahon G, Kemp JP, Northstone K, Rahi JS, Cumberland PM, Martin NG, Sanfilippo PG, Lu Y, Wang YX, Hayward C, Polašek O, Campbell H, Bencic G, Wright AF, Wedenoja J, Zeller T, Schillert A, Mirshahi A, Lackner K, Yip SP, Yap MK, 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 YY, Tai ES, Vithana E, Barathi V, Zheng Y, Siantar RG, Neelam K, Shin Y, Lam J, Yonova-Doing E, Venturini C, Hosseini SM, Wong HS, Lehtimäki T, Kähönen M, Raitakari O, Timpson NJ, Evans DM, Khor CC, Aung T, Young TL, Mitchell P, Klein B, van Duijn CM, Meitinger T, Jonas JB, Baird PN, Mackey DA, Wong TY, Saw SM, Pärssinen O, Stambolian D, Hammond CJ, Klaver CC, Williams C, Paterson AD, Bailey-Wilson JE, and Guggenheim JA
Subjects: Adult, Age Factors, Asian People, Astigmatism pathology, Calcium-Binding Proteins, Cohort Studies, Female, Genetic Markers, Humans, Male, Middle Aged, Neural Cell Adhesion Molecules, White People, Astigmatism genetics, Cell Adhesion Molecules, Neuronal genetics, Genome-Wide Association Study, High Mobility Group Proteins genetics, Nerve Tissue Proteins genetics
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
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32. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

Author: Cheng CY, Schache M, Ikram MK, Young TL, Guggenheim JA, Vitart V, MacGregor S, Verhoeven VJ, Barathi VA, Liao J, Hysi PG, Bailey-Wilson JE, St Pourcain B, Kemp JP, McMahon G, Timpson NJ, Evans DM, Montgomery GW, Mishra A, Wang YX, Wang JJ, Rochtchina E, Polasek O, Wright AF, Amin N, van Leeuwen EM, Wilson JF, Pennell CE, van Duijn CM, de Jong PT, Vingerling JR, Zhou X, Chen P, Li R, Tay WT, Zheng Y, Chew M, Burdon KP, Craig JE, Iyengar SK, Igo RP Jr, Lass JH Jr, Chew EY, Haller T, Mihailov E, Metspalu A, Wedenoja J, Simpson CL, Wojciechowski R, Höhn R, Mirshahi A, Zeller T, Pfeiffer N, Lackner KJ, Bettecken T, Meitinger T, Oexle K, Pirastu M, Portas L, Nag A, Williams KM, Yonova-Doing E, Klein R, Klein BE, Hosseini SM, Paterson AD, Makela KM, Lehtimaki T, Kahonen M, Raitakari O, Yoshimura N, Matsuda F, Chen LJ, Pang CP, Yip SP, Yap MK, Meguro A, Mizuki N, Inoko H, Foster PJ, Zhao JH, Vithana E, Tai ES, Fan Q, Xu L, Campbell H, Fleck B, Rudan I, Aung T, Hofman A, Uitterlinden AG, Bencic G, Khor CC, Forward H, Pärssinen O, Mitchell P, Rivadeneira F, Hewitt AW, Williams C, Oostra BA, Teo YY, Hammond CJ, Stambolian D, Mackey DA, Klaver CC, Wong TY, Saw SM, and Baird PN
Subjects: Adolescent, Adult, Aged, Asian People, Axial Length, Eye pathology, Eye Proteins metabolism, Female, Gene Expression, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Refractive Errors ethnology, Refractive Errors pathology, Signal Transduction, White People, Axial Length, Eye metabolism, Eye Proteins genetics, Genetic Loci, Genetic Predisposition to Disease, Refractive Errors genetics
Abstract: Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Published: 2013
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32 results on '"Yonova-Doing, E"'

1. Stroke genetics informs drug discovery and risk prediction across ancestries

2. Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)

3. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries (Nature, (2022), 611, 7934, (115-123), 10.1038/s41586-022-05165-3)

4. Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

5. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

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

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

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

9. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

10. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

11. Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke

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

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

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

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

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

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

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

19. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries.

20. Stroke genetics informs drug discovery and risk prediction across ancestries.

21. Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.

22. Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion.

23. Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.

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

25. Author Correction: Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.

26. Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.

27. Phenotypic and genotypic correlation between myopia and intelligence.

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

29. Do twins share the same dress code? Quantifying relative genetic and environmental contributions to subjective perceptions of "the dress" in a classical twin study.

30. The correlation between cognitive performance and retinal nerve fibre layer thickness is largely explained by genetic factors.

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

32. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

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32 results on '"Yonova-Doing, E"'

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