Author: "Vukcevic D" - Searchworks@Jio Institute Digital Library Search Results

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117 results on '"Vukcevic D"'

1. Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest

Author: Pappas, DJ, Lizee, A, Paunic, V, Beutner, KR, Motyer, A, Vukcevic, D, Leslie, S, Biesiada, J, Meller, J, Taylor, KD, Zheng, X, Zhao, LP, Gourraud, P-A, Hollenbach, JA, Mack, SJ, and Maiers, M
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Human Genome, Genetics, Generic health relevance, Alleles, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genotype, HLA Antigens, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, HLA-DRB1 Chains, Haplotypes, Humans, Polymorphism, Single Nucleotide, White People, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract: Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall,
Published: 2018

2. Ballot-Polling Audits of Instant-Runoff Voting Elections with a Dirichlet-Tree Model

Author: Everest, F, Blom, M, Stark, PB, Stuckey, PJ, Teague, V, Vukcevic, D, Everest, F, Blom, M, Stark, PB, Stuckey, PJ, Teague, V, and Vukcevic, D
Published: 2023

3. Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1

Author: Kouyos, RD, Harrison, GR, Leaton, LAA, Harrison, E, Kichula, K, Viken, MJ, Shortt, J, Gignoux, C, Lie, B, Vukcevic, D, Leslie, S, Norman, P, Kouyos, RD, Harrison, GR, Leaton, LAA, Harrison, E, Kichula, K, Viken, MJ, Shortt, J, Gignoux, C, Lie, B, Vukcevic, D, Leslie, S, and Norman, P
Abstract: Highly polymorphic interaction of KIR3DL1 and KIR3DS1 with HLA class I ligands modulates the effector functions of natural killer (NK) cells and some T cells. This genetically determined diversity affects severity of infections, immune-mediated diseases, and some cancers, and impacts the course of immunotherapies, including transplantation. KIR3DL1 is an inhibitory receptor, and KIR3DS1 is an activating receptor encoded by the KIR3DL1/S1 gene that has more than 200 diverse and divergent alleles. Determination of KIR3DL1/S1 genotypes for medical application is hampered by complex sequence and structural variation, requiring targeted approaches to generate and analyze high-resolution allele data. To overcome these obstacles, we developed and optimized a model for imputing KIR3DL1/S1 alleles at high-resolution from whole-genome SNP data. We designed the model to represent a substantial component of human genetic diversity. Our Global imputation model is effective at genotyping KIR3DL1/S1 alleles with an accuracy ranging from 88% in Africans to 97% in East Asians, with mean specificity of 99% and sensitivity of 95% for alleles >1% frequency. We used the established algorithm of the HIBAG program, in a modification named Pulling Out Natural killer cell Genomics (PONG). Because HIBAG was designed to impute HLA alleles also from whole-genome SNP data, PONG allows combinatorial diversity of KIR3DL1/S1 with HLA-A and -B to be analyzed using complementary techniques on a single data source. The use of PONG thus negates the need for targeted sequencing data in very large-scale association studies where such methods might not be tractable.
Published: 2022

4. Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA‐DRB1

Author: Martino, D. J., Ashley, S., Koplin, J., Ellis, J., Saffery, R., Dharmage, S. C., Gurrin, L., Matheson, M. C., Kalb, B., Marenholz, I., Beyer, K., Lee, Y.A., Hong, X., Wang, X., Vukcevic, D., Motyer, A., Leslie, S., Allen, K. J., and Ferreira, M. A. R.
Published: 2017
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5. Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Author: Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., S. M. E., Ng, Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., S. M., Ng, Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., Ng, S. M. E., Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., Ng, S. M., Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Daly, Mark J. [0000-0002-0949-8752], Apollo - University of Cambridge Repository, Hugot, Jean-Pierre [0000-0002-8446-6056], UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, Romagnoni, A, Jegou, S, VAN STEEN, Kristel, Wainrib, G, Hugot, JP, Peyrin-Biroulet, L, Chamaillard, M, Colombel, JF, Cottone, M, D'Amato, M, D'Inca, R, Halfvarson, J, Henderson, P, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Ng, SME, Oikonomou, I, Peeters, H, Proctor, DD, Rahier, JF, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Andrews, JM, Bampton, PA, Barclay, M, Florin, TH, Gearry, R, Krishnaprasad, K, Lawrance, IC, Mahy, G, Montgomery, GW, Radford-Smith, G, Roberts, RL, Simms, LA, Hanigan, K, Croft, A, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie, AM, Beck, K, Bernard, EJ, Binion, DG, Bitton, A, Brant, SR, Cho, JH, Cohen, A, Croitoru, K, Daly, MJ, Datta, LW, Deslandres, C, Duerr, RH, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, GR, Haritunians, T, Jobin, G, Katz, S, Lahaie, RG, McGovern, DP, Nelson, L, Ng, SM, Ning, K, Pare, P, Regueiro, MD, Rioux, JD, Ruggiero, E, Schumm, LP, Schwartz, M, Scott, R, Sharma, Y, Silverberg, MS, Spears, D, Steinhart, AH, Stempak, JM, Swoger, JM, Tsagarelis, C, Zhang, C, Zhao, HY, AERTS, Jan, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barnes, C, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, CM, Coffey, AJ, Mc Connell, J, Conrad, DF, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Frayling, TM, Freathy, RM, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Marchini, JL, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, McVean, G, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Munroe, PB, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Ovington, NR, Owen, MJ, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, JRB, Phillips, A, Plagnol, V, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Sawcer, SJ, Schuilenburg, H, Scott, CE, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stirrups, K, Stone, MA, Strachan, DP, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Tobin, MD, Travers, ME, Turnbull, C, Vukcevic, D, Wain, LV, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Yau, C, Young, AH, Zeggini, E, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Hurles, ME, Duncanson, A, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Kwiatkowski, DP, McCarthy, MI, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Jankowski, J, Markus, HS, Palmer, CNA, Plomin, R, Rautanen, A, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, and Kwiatkowski, D
Subjects: Male, 692/4020/1503/257/1402, Genotype, Genotyping Techniques, LOCI, 45/43, lcsh:Medicine, Polymorphism, Single Nucleotide, Crohn's disease, genetics, genome wide association, Article, Deep Learning, Crohn Disease, INDEL Mutation, Genetics research, Humans, genetics, Genetic Predisposition to Disease, 129, lcsh:Science, Alleles, Science & Technology, genome wide association, RISK PREDICTION, 45, Models, Genetic, lcsh:R, Decision Trees, 692/308/2056, ASSOCIATION, Multidisciplinary Sciences, Crohn's disease, Logistic Models, Nonlinear Dynamics, ROC Curve, Area Under Curve, Science & Technology - Other Topics, lcsh:Q, Female, Neural Networks, Computer, INFLAMMATORY-BOWEL-DISEASE, Genome-Wide Association Study
Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers. Tis work was supported by Fondation pour la Recherche Médical (ref DEI20151234405) and Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. Te authors thank the students that participated to the wisdom of the crowd exercise.
Published: 2019

6. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Author: Lyons, P. A., Peters, J. E., Alberici, F., Liley, J., Coulson, R. M. R., Astle, W., Baldini, C., Bonatti, F., Cid, María Cinta, Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D. R. W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M. A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G. A., Rewerska, B., Schett, George, Sinico, R. A., Szczeklik, W., Tesar, Vladimir, Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A. S., Bruce, I., Clarkson, M., Conlon, N., DasGupta, B., Doulton, T. W. R., Espígol-Frigolé, Georgina, Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernández Rodríguez, José, Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A. A., Marguerie, C., Maritati, F., Marvisi, C., McHugh, N. J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, Leonid, Pesci, Alberto, Prieto-Gonzalez, S., Ramentol-Sintas, Marc, Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans, Roser, Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R. A., Vaglio, A., Holle, J. U., Wallace, C., Smith, K. G. C., Universitat Autònoma de Barcelona, Lyons, P. A., Peters, J. E., Alberici, F., Liley, J., Coulson, R. M. R., Astle, W., Baldini, C., Bonatti, F., Cid, M. C., Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D. R. W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M. A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G. A., Rewerska, B., Schett, G., Sinico, R. A., Szczeklik, W., Tesar, V., Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A. S., Bruce, I., Clarkson, M., Conlon, N., Dasgupta, B., Doulton, T. W. R., Espigol-Frigole, G., Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernandez-Rodriguez, J., Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A. A., Marguerie, C., Maritati, F., Marvisi, C., Mchugh, N. J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, L., Pesci, A., Prieto-Gonzalez, S., Ramentol-Sintas, M., Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans-Laque, R., Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R. A., Vaglio, A., Holle, J. U., Wallace, C., Smith, K. G. C., Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, and United Kingdom Research and Innovation
Subjects: 0301 basic medicine, Candidate gene, Antineutrophil Cytoplasmic, General Physics and Astronomy, Genome-wide association study, Autoimmunity, Genome-wide association studies, 0302 clinical medicine, Rheumatic diseases, immune system diseases, Eosinophilic, Eosinophilia, lcsh:Science, education.field_of_study, Multidisciplinary, Genome-wide association, eosinophilic granulomatosis with polyangiitis, ANCA status, 3. Good health, medicine.symptom, Vasculitis, Granulomatosis with polyangiitis, Antibodies, Antineutrophil Cytoplasmic, Eosinophils, Genetic Association Studies, Granulomatosis with Polyangiitis, Humans, Mendelian Randomization Analysis, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, European Vasculitis Genetics Consortium, Science, Population, General Biochemistry, Genetics and Molecular Biology, Article, Antibodies, 03 medical and health sciences, medicine, Immunogenetics, education, Rheumatology and Autoimmunity, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, Reumatologi och inflammation, business.industry, General Chemistry, medicine.disease, respiratory tract diseases, 030104 developmental biology, Immunology, EGPA, HLA, ANCA, genetics, lcsh:Q, business
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA., Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).
Published: 2019
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7. Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype

Author: Craddock, N, Jones, L, Jones, I R, Kirov, G, Green, E K, Grozeva, D, Moskvina, V, Nikolov, I, Hamshere, M L, Vukcevic, D, Caesar, S, Gordon-Smith, K, Fraser, C, Russell, E, Norton, N, Breen, G, St Clair, D, Collier, D A, Young, A H, Ferrier, I N, Farmer, A, McGuffin, P, Holmans, P A, Donnelly, P, Owen, M J, and O'Donovan, M C
Published: 2010
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8. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author: Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, R, Jenkins, S, Jenko, M, Jimenez, R, Jimenez Gomez, B, Joachim, S, Joelsson-Alm, E, John, J, Jonikaite, L, Jovic, M, Jungwirth, B, Junke, E, Kabakov, B, Kadaoui, S, Kanski, A, Karadag, S, Karbonskiene, A, Karjagin, J, Kasnik, D, Katanolli, F, Katsika, E, Kaufmann, K, Keane, H, Kelly, M, Kent, M, Keraitiene, G, Khudhur, A, Khuenl-Brady, K, Kidd, L, King, S, Kirchgassner, K, Klancir, T, Klucniks, A, Knotzer, J, Knowlden, P, Koers, L, Kompan, J, Koneti, K, Kooij, F, Koolen, E, Koopman - van Gemert, A, Kopp, K, Korfiotis, D, Korolkov, O, Kosinova, M, Kostenberger, M, Kotzinger, O, Kovacevic, M, Kranke, P, Kranke, E, Kraus, C, Kraus, S, Kubitzek, C, Kucharski, R, Kucukguclu, S, Kudrashou, A, Kumar, V, Kummen, L, Kunit, C, Kushakovsky, V, Kuvaki, B, Kuzmanovska, B, Kyttari, A, Landoni, G, Lau, G, Lazarev, K, Legett, S, Legrottaglie, A, Leonardi, S, Leong, M, Lercher, H, Leuvrey, M, Leva, B, Levstek, M, Limb, J, Lindholm, E, Linton, F, Liperi, C, Lipski, F, Lirk, P, Lisi, A, Liskova, K, Lluch Oltra, A, Loganathan, V, Lombardi, S, Lopez, E, Lopez Rodriguez, M, Lorenzini, L, Lowicka, M, Lugovoy, A, Luippold, M, Lumb, A, Macas, A, Macgregor, M, Machado, H, Maciariello, M, Madeira, I, Maitan, S, Majewski, J, Maldini, B, Malewski, G, Manfredini, L, Manner, O, Marchand, B, Marcu, A, Margalef, J, Margarson, M, Marinheiro, L, Markic, A, Markovic Bozic, J, Marrazzo, F, Martin, J, Martin Ayuso, M, Martinez, E, Martino, E, Martinson, V, Marusic-Gaser, K, Mascarenhas, C, Mathis, C, Matsota, P, Mavrommati, E, Mazul Sunko, B, Mccourt, K, Mcgill, N, Mckee, R, Meco, B, Meier, S, Melbourne, S, Melbybrathen, G, Meli, A, Melia, A, Melotti, R, Menga, M, Mercer, P, Merotra, S, Mescolini, S, Metterlein, T, Michalov, M, Michlig, S, Midgley, S, Milic, M, Milojevic, M, Minana, A, Minto, G, Mirabella, L, Mirea, L, Mittelstadt, L, Moeglen, A, Moise, A, Mokini, Z, Molin, A, Molto, L, Monea, M, Montalto, F, Montgomery, J, Montgomery, C, Montillo, G, Moore, S, Moore, F, Moreira, Z, Moreno, T, Moreno, R, Moret, E, Moreton, S, Morgan, M, Moro Velasco, C, Morri, D, Moull, A, Moura, F, Mraz, P, Mrozek, K, Mukhtar, K, Muniyappa, S, Murray, H, Murthy, B, Mushambi, M, Nadolski, M, Nardelli, P, Nardin, G, Navarro Perez, R, Naveiro, A, Negri, M, Nesek Adam, V, Neskovic, V, Neuwersch, S, Neves, M, Nguyen, B, Ni Eochagain, A, Nicholas, C, Nightingale, J, Norrie, K, Novak-Jankovic, V, Novakova, A, Novillo, M, Numan, S, Oduro-Dominah, L, Oldner, A, Oliveira, I, Ologoiu, D, Oloktsidou, I, O'Reilly, R, Orlando, A, Ovezov, A, Ozbilgin, S, Paal, P, Padin Barreiro, L, Palugniok, R, Papaioannou, A, Papapostolou, K, Paranthaman, P, Pardey Bracho, G, Parente, S, Parfeni, A, Pasin, L, Passey, S, Pastor, E, Patch, S, Patil, A, Paunescu, M, Pehboeck, D, Pereira, M, Pereira, C, Perez Caballero, P, Perez Garcia, A, Perez Soto, A, Perez Tejero, G, Perez-Cerda, F, Pesenti, A, Petta, R, Philippe, S, Pickering, D, Pico Veloso, J, Pina, P, Pinho-Oliveira, V, Pinol, S, Pinto, R, Pistidda, L, Pitterle, M, Piwowarczyk, P, Plotnikova, O, Pohl, H, Poldermann, J, Polkovicova, L, Pompei, L, Popescu, M, Popovic, R, Pota, V, Potocnik, M, Potrec, B, Potter, A, Pramod, N, Prchalova, M, Preckel, B, Pugh, R, Pulletz, M, Radoeshki, A, Rafi, A, Ragazzi, R, Raineri Santi, M, Rajamanickam, T, Rajput, Z, Ramachandran, R, Ramasamy, R, Ramessur, S, Rao, R, Rasmussen, A, Rato, A, Razaque, U, Real Navacerrada, M, Reavley, C, Reid, J, Reschreiter, H, Rial, E, Ribas Carrasco, P, Ribeiro, S, Rich, N, Richardson, L, Rimaitis, K, Rimaitis, M, Ringvold, E, Ripke, F, Ristescu, I, Ritchie, K, Rodenas, F, Rodrigues, P, Rogers, E, Rogerson, D, Romagnoli, S, Romero, E, Rondovic, G, Rose, B, Roth, W, Rotter, M, Rousseau, G, Rudjord, A, Rueffert, H, Rundgren, M, Rupprecht, K, Rushton, A, Russotto, V, Rypulak, E, Ryszka, M, Sa, J, Sa Couto, P, Saby, S, Sagic, J, Saleh, O, Sales, G, Sanchez Sanchez, Y, Sanghera, S, Sanli Karip, C, Santiveri Papiol, F, Santos, S, Sarno, S, Saul, D, Saunders, D, Savic, N, Scalco, L, Scanlon, D, Schaller, S, Schax, C, Scheffer, G, Schening, A, Schiavone, V, Schmidt-Ehrenberg, F, Schmidt-Mutter, C, Schonberg, C, Schopflin, C, Schreiber, J, Schultz, M, Schurig, M, Scott, C, Sebestian, S, Sehgal, S, Sem, V, Semenas, E, Serafini, E, Serchan, P, Shields, M, Shobha, R, Shosholcheva, M, Siamansour, T, Siddaiah, N, Siddiqi, K, Sinclair, R, Singh, P, Singh, R, Sinha, A, Skinner, A, Smee, E, Smekalova, O, Smith, N, Smith, T, Smitz, C, Smole, D, Sojcic, N, Soler Pedrola, M, Somanath, S, Sonksen, J, Sorella, M, Sormus, A, Soro, M, Soto, C, Spada, A, Spadaro, S, Spaeth, J, Sparr, H, Spielmann, A, Spindler-Vesel, A, Stamelos, M, Stancombe L, L, Stanculescu, A, Standl, T, Standley, T, Stanek, O, Stanisavljevic, S, Starczewska, M, Stauble, C, Steen, J, Stefan, O, Stell, E, Stera, C, Stevens, M, Stoerckel, M, Stosic, B, Stourac, P, Stroumpoulis, K, Struck, R, Suarez de la Rica, A, Sultanpori, A, Sundara Rajan, R, Suying, O, Svensen, C, Swan, L, Syrogianni, P, Sysiak, J, Szederjesi, J, Taddei, S, Tan Hao, E, Tanou, V, Tarabova, K, Tardaguila Sancho, P, Tarroso, M, Tartaglione, M, Taylor, E, Tbaily, L, Telford, R, Terenzoni, M, Theodoraki, K, Thornley, H, Tiganiuc, L, Toim, H, Tomescu, D, Tommasino, C, Toni, J, Toninelli, A, Toretti, I, Townley, S, Trepenaitis, D, Trethowan, B, Tsaousi, G, Tsiftsi, A, Tudor, A, Turan, G, Turhan, S, Unic-Stojanovic, D, Unterbuchner, C, Unzueta, C, Uranjek, J, Ursic, T, Vaida, S, Valldeperas Ferrer, S, Valldeperas Hernandez, M, Valsamidis, D, Van Beek, R, Van dasselaer, N, Van Der Beek, T, Van Duivenvoorde, Y, van Klei, W, Van Poorter, F, Van Zaane, B, Van Zundert, T, Van Zyl, R, Vargas Munoz, A, Varsani, N, Vasconcelos, P, Vassilakis, G, Vecchiatini, T, Vecera, L, Vercauteren, M, Verdouw, B, Verheyen, V, Verri, M, Vicari Sottosanti, L, Vico, M, Vidal Mitjans, P, Vilardi, A, Vissicchio, D, Vitale, G, Vitkovic, B, Vizcaychipi, M, Voicu, A, Voje, M, Volfova, I, Volta, C, Von Lutterotti, T, von Tiesenhausen, A, Vrecic-Slabe, S, Vukcevic, D, Vukovic, R, Vullo, P, Wade, A, Wallberg, H, Wallden, J, Wallner, J, Walther Sturesson, L, Watson, D, Weber, S, Wegiel Leskiewiq, A, Weller, D, Wensing, C, Werkmann, M, Westberg, H, Wikstrom, E, Williams, B, Wilson, R, Wirth, S, Wittmann, M, Wood, L, Wright, S, Zachoval, C, Zambon, M, Zampieri, S, Zampone, S, Zangrillo, A, Zani, G, Zavackiene, A, Zieglerder, R, Zonneveldt, H, Zsisku, L, Zucker, T, Zukowski, M, Zuleika, M, Zupaneie, D, Kirmeier E., Eriksson L. I., Lewald H., Jonsson Fagerlund M., Hoeft A., Hollmann M., Meistelman C., Hunter J. M., Ulm K., Blobner M., Abad Gurumeta A., Abernethy C., Abigail P., Achaibar K., Adam E., Afshari A., Agudelo Montoya M. E., Akgun F. N., Aletti G., Alkis N., Allan K., Allan A., Allaouchiche B., Allcock C., Almasy E., Amey I., Amigoni M., Andersen E., Andersson P., Anipchenko N., Antunes P., Armstrong E., Aslam T. N., Aslin B., Assuncao J. P., Ausserer J., Avvai M., Awad N., Ayas Montero B., Ayuso M., Azevedo P., Badarau V., Badescu R., Baiardo Redaelli M., Baird C., Baird Y., Baker T., Balaji P., Balan C., Balandin A., Balescu-Arion C., Baliuliene V., Baltasar Isabel J., Baluch S. N., Bandrabur D., Bankewitz C., Barber K., Barbera F., Barcraft-Barnes H., Barletti V., Barnett G., Baron K., Barros A., Barsan V., Bartlett P., Batistaki C., Baumgarten G., Baytas V., Beauchamp N., Becerra Cayetano I. A., Bell S., Bellandi M., Belletti A., Belmonte Cuenca J., Benitez-Cano A., Beretta L., Berger M., Bergmann N., Bergmark K., Bermudez Lopez M., Bernotaite M., Beurskens C., Bidd H., Bifulco F., Bignami E., Bilic A., Bilskiene D., Bischoff P., Bishop L., Bjonness T., Blaylock H., Blethyn K., Blincoe T., Blokhin I., Blunt N., Boer C., Bois G., Bonicolini E., Booth J., Borecka-Kedzierska M., Borstnar K., Borys M., Boselli E., Bouvet L., Bouwman A., Bowen L., Bowrey S., Boxall L., Bozic T., Bradley T., Branco T., Brazzi L., Brazzoni M., Brear T., Brogly N., Brohi F., Broms J., Bubliauskas A., Bucolo G. E., Buerkle H., Buggy D., Buhre W., Bukauskas T., Butturini F., Byttner A., Cabrera Diaz I., Calderon A., Calhau R., Callejo A., Cammu G., Campesato M., Can O. S., Candeias M., Cantor A., Carise E., Carmona C., Carreteiro J., Carrieri C., Carter A., Casal M., Casanova I., Cascella M., Casero L. M., Casiraghi G. M., Castelo-Branco L., Castro Arranz C., Cernea D. D., Cervantes J., Chandler B., Charnock R., Chatzimicali A., Chinery E., Chishti A., Chondhury P., Christie E., Christodoudiles G., Ciardo S., Cimpeanu L., Cindea I., Cinnella G., Clark S., Clayton M., Cocu S., Collyer T., Colvin C., Cope S., Copeta F., Copotoiu S. -M., Correia de Barros F., Corso R. M., Cortegiani A., Costa G., Cowton A., Cox N., Craig J., Cricca V., Cronin J., Cunha M., Cuomo A., Curley K., Czuczwar M., Dabrowska D., Damster S., Danguy des Deserts M., Daniliuc A., Danninger T., Darwish I., Dascalu C., Davies K., Davies S., De Boer H., De Flaviis A., De Selincourt G., Deana C., Debaene B., Debreceni G., Dedhia J., Delgado Garcia I., Della Rocca G., Delroy-Buelles L., Desai T., Dhillon P., Di Giacinto I., Di Mauro P., Diaz Gomez T. V., Dimitrovski A., Dinic V., Dirzu D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurnakova P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil J., Fernandez Castineira A., Fernandez Castineira J., Fernando A., Ferrando C., Ferreira L., Ferreira P., Feyling A., Filipescu D., Fleischer A., Floris L., Foerster U., Fox B., Franke U., Frasca D., Frey C., Frost V., Fullin G., Fumagalli J., Furneval J., Fusari M., Gallacher S., Galushka S., Gambale G., Gambino I., Garcia-Perez M. L., Garg S., Garlak J., Gavranovic Z., Gavrilov R., Gaynor L., Gecaj Gashi A., Georghiou M., Gerjevic B., Gferer G., Giarratano A., Gibson A., Gievski V., Giles J., Gillberg L., Gilowska K., Gilsanz Rodriguez F., Gioia A., Giovannoni C., Girotra V., Gkinas D., Gkiokas G., Godoroja D., Goebel U., Goel V., Gonzalez M., Goranovic T., Gornik-Wlaszczuk E., Gosavi S., Gottfridsson P., Gottschalk A., Granell M., Granstrom A., Grassetto A., Greenwood A., Grigoras I., Grintescu I., Gritsan A., Gritsan G., Grynyuk A., Guadagnin G. M., Guarnieri M., Guclu C., Guerrero Diez M., Gunenc F., Gunther U., Gupta P., Guttenthaler V., Hack Y., Hafisayena A., Hagau N., Haldar J., Hales D., Hanci V., Hanna-Jumma S., Harazim H., Harlet P., Harper D., Harris B., Harvey O., Hashimi M., Hawkins L., Hayes C., Heaton J., Heier T., Helliwell L., Hemmes S., Henderson K., Hermanides J., Hermanns H., Herrera Hueso B., Hestenes S., Hettiarachchi R., Highgate J., Hodgson K., Hoelbling D., Holland J., Horhota L., Hormis A., Hribar R., Hua A., Humphreys S., Humphries R., Humplikova S., Hunt J., Husnain A., Hussein A., Hyams B., Iannuccelli F., Ilette K., Ilyas C., Inan T., India I., Ionitav V., Irwin F., Jain V., Janez B., Jankovic R., Jenkins S., Jenko M., Jimenez R., Jimenez Gomez B., Joachim S., Joelsson-Alm E., John J., Jonikaite L., Jovic M., Jungwirth B., Junke E., Kabakov B., Kadaoui S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgassner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert A. W. M. M., Kopp K., Korfiotis D., Korolkov O., Kosinova M., Kostenberger M., Kotzinger O., Kovacevic M., Kranke P., Kranke E., Kraus C., Kraus S., Kubitzek C., Kucharski R., Kucukguclu S., Kudrashou A., Kumar V., Kummen L., Kunit C., Kushakovsky V., Kuvaki B., Kuzmanovska B., Kyttari A., Landoni G., Lau G., Lazarev K., Legett S., Legrottaglie A. M., Leonardi S., Leong M., Lercher H., Leuvrey M., Leva B., Levstek M., Limb J., Lindholm E., Linton F., Liperi C., Lipski F., Lirk P., Lisi A., Liskova K., Lluch Oltra A., Loganathan V., Lombardi S., Lopez E., Lopez Rodriguez M., Lorenzini L., Lowicka M., Lugovoy A., Luippold M., Lumb A., Macas A., Macgregor M., Machado H., Maciariello M., Madeira I., Maitan S., Majewski J., Maldini B., Malewski G., Manfredini L., Manner O., Marchand B., Marcu A., Margalef J., Margarson M., Marinheiro L., Markic A., Markovic Bozic J., Marrazzo F., Martin J., Martin Ayuso M., Martinez E., Martino E. A., Martinson V., Marusic-Gaser K., Mascarenhas C., Mathis C., Matsota P., Mavrommati E., Mazul Sunko B., McCourt K., McGill N., McKee R., Meco B. C., Meier S., Melbourne S., Melbybrathen G., Meli A., Melia A., Melotti R. M., Menga M. R., Mercer P., Merotra S., Mescolini S., Metterlein T., Michalov M., Michlig S., Midgley S., Milic M., Milojevic M., Minana A., Minto G., Mirabella L., Mirea L., Mittelstadt L., Moeglen A., Moise A., Mokini Z., Molin A., Molto L., Monea M. C., Montalto F., Montgomery J., Montgomery C., Montillo G., Moore S., Moore F., Moreira Z., Moreno T., Moreno R., Moret E., Moreton S., Morgan M., Moro Velasco C., Morri D., Moull A., Moura F., Mraz P., Mrozek K., Mukhtar K., Muniyappa S., Murray H., Murthy B. V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. I., Reavley C., Reid J., Reschreiter H., Rial E., Ribas Carrasco P., Ribeiro S., Rich N., Richardson L., Rimaitis K., Rimaitis M., Ringvold E. -M., Ripke F., Ristescu I., Ritchie K., Rodenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sa J., Sa Couto P., Saby S., Sagic J., Saleh O., Sales G., Sanchez Sanchez Y., Sanghera S., Sanli Karip C., Santiveri Papiol F. J., Santos S., Sarno S., Saul D., Saunders D., Savic N., Scalco L., Scanlon D., Schaller S., Schax C., Scheffer G. J., Schening A., Schiavone V., Schmidt-Ehrenberg F., Schmidt-Mutter C., Schonberg C., Schopflin C., Schreiber J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojcic N., Soler Pedrola M., Somanath S., Sonksen J., Sorella M. C., Sormus A., Soro M., Soto C., Spada A., Spadaro S., Spaeth J., Sparr H., Spielmann A., Spindler-Vesel A., Stamelos M., Stancombe L L., Stanculescu A., Standl T., Standley T., Stanek O., Stanisavljevic S., Starczewska M., Stauble C., Steen J., Stefan O. M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., Zupaneie D., Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, R, Jenkins, S, Jenko, M, Jimenez, R, Jimenez Gomez, B, Joachim, S, Joelsson-Alm, E, John, J, Jonikaite, L, Jovic, M, Jungwirth, B, Junke, E, Kabakov, B, Kadaoui, S, Kanski, A, Karadag, S, Karbonskiene, A, Karjagin, J, Kasnik, D, Katanolli, F, Katsika, E, Kaufmann, K, Keane, H, Kelly, M, Kent, M, Keraitiene, G, Khudhur, A, Khuenl-Brady, K, Kidd, L, King, S, Kirchgassner, K, Klancir, T, Klucniks, A, Knotzer, J, Knowlden, P, Koers, L, Kompan, J, Koneti, K, Kooij, F, Koolen, E, Koopman - van Gemert, A, Kopp, K, Korfiotis, D, Korolkov, O, Kosinova, M, Kostenberger, M, Kotzinger, O, Kovacevic, M, Kranke, P, Kranke, E, Kraus, C, Kraus, S, Kubitzek, C, Kucharski, R, Kucukguclu, S, Kudrashou, A, Kumar, V, Kummen, L, Kunit, C, Kushakovsky, V, Kuvaki, B, Kuzmanovska, B, Kyttari, A, Landoni, G, Lau, G, Lazarev, K, Legett, S, Legrottaglie, A, Leonardi, S, Leong, M, Lercher, H, Leuvrey, M, Leva, B, Levstek, M, Limb, J, Lindholm, E, Linton, F, Liperi, C, Lipski, F, Lirk, P, Lisi, A, Liskova, K, Lluch Oltra, A, Loganathan, V, Lombardi, S, Lopez, E, Lopez Rodriguez, M, Lorenzini, L, Lowicka, M, Lugovoy, A, Luippold, M, Lumb, A, Macas, A, Macgregor, M, Machado, H, Maciariello, M, Madeira, I, Maitan, S, Majewski, J, Maldini, B, Malewski, G, Manfredini, L, Manner, O, Marchand, B, Marcu, A, Margalef, J, Margarson, M, Marinheiro, L, Markic, A, Markovic Bozic, J, Marrazzo, F, Martin, J, Martin Ayuso, M, Martinez, E, Martino, E, Martinson, V, Marusic-Gaser, K, Mascarenhas, C, Mathis, C, Matsota, P, Mavrommati, E, Mazul Sunko, B, Mccourt, K, Mcgill, N, Mckee, R, Meco, B, Meier, S, Melbourne, S, Melbybrathen, G, Meli, A, Melia, A, Melotti, R, Menga, M, Mercer, P, Merotra, S, Mescolini, S, Metterlein, T, Michalov, M, Michlig, S, Midgley, S, Milic, M, Milojevic, M, Minana, A, Minto, G, Mirabella, L, Mirea, L, Mittelstadt, L, Moeglen, A, Moise, A, Mokini, Z, Molin, A, Molto, L, Monea, M, Montalto, F, Montgomery, J, Montgomery, C, Montillo, G, Moore, S, Moore, F, Moreira, Z, Moreno, T, Moreno, R, Moret, E, Moreton, S, Morgan, M, Moro Velasco, C, Morri, D, Moull, A, Moura, F, Mraz, P, Mrozek, K, Mukhtar, K, Muniyappa, S, Murray, H, Murthy, B, Mushambi, M, Nadolski, M, Nardelli, P, Nardin, G, Navarro Perez, R, Naveiro, A, Negri, M, Nesek Adam, V, Neskovic, V, Neuwersch, S, Neves, M, Nguyen, B, Ni Eochagain, A, Nicholas, C, Nightingale, J, Norrie, K, Novak-Jankovic, V, Novakova, A, Novillo, M, Numan, S, Oduro-Dominah, L, Oldner, A, Oliveira, I, Ologoiu, D, Oloktsidou, I, O'Reilly, R, Orlando, A, Ovezov, A, Ozbilgin, S, Paal, P, Padin Barreiro, L, Palugniok, R, Papaioannou, A, Papapostolou, K, Paranthaman, P, Pardey Bracho, G, Parente, S, Parfeni, A, Pasin, L, Passey, S, Pastor, E, Patch, S, Patil, A, Paunescu, M, Pehboeck, D, Pereira, M, Pereira, C, Perez Caballero, P, Perez Garcia, A, Perez Soto, A, Perez Tejero, G, Perez-Cerda, F, Pesenti, A, Petta, R, Philippe, S, Pickering, D, Pico Veloso, J, Pina, P, Pinho-Oliveira, V, Pinol, S, Pinto, R, Pistidda, L, Pitterle, M, Piwowarczyk, P, Plotnikova, O, Pohl, H, Poldermann, J, Polkovicova, L, Pompei, L, Popescu, M, Popovic, R, Pota, V, Potocnik, M, Potrec, B, Potter, A, Pramod, N, Prchalova, M, Preckel, B, Pugh, R, Pulletz, M, Radoeshki, A, Rafi, A, Ragazzi, R, Raineri Santi, M, Rajamanickam, T, Rajput, Z, Ramachandran, R, Ramasamy, R, Ramessur, S, Rao, R, Rasmussen, A, Rato, A, Razaque, U, Real Navacerrada, M, Reavley, C, Reid, J, Reschreiter, H, Rial, E, Ribas Carrasco, P, Ribeiro, S, Rich, N, Richardson, L, Rimaitis, K, Rimaitis, M, Ringvold, E, Ripke, F, Ristescu, I, Ritchie, K, Rodenas, F, Rodrigues, P, Rogers, E, Rogerson, D, Romagnoli, S, Romero, E, Rondovic, G, Rose, B, Roth, W, Rotter, M, Rousseau, G, Rudjord, A, Rueffert, H, Rundgren, M, Rupprecht, K, Rushton, A, Russotto, V, Rypulak, E, Ryszka, M, Sa, J, Sa Couto, P, Saby, S, Sagic, J, Saleh, O, Sales, G, Sanchez Sanchez, Y, Sanghera, S, Sanli Karip, C, Santiveri Papiol, F, Santos, S, Sarno, S, Saul, D, Saunders, D, Savic, N, Scalco, L, Scanlon, D, Schaller, S, Schax, C, Scheffer, G, Schening, A, Schiavone, V, Schmidt-Ehrenberg, F, Schmidt-Mutter, C, Schonberg, C, Schopflin, C, Schreiber, J, Schultz, M, Schurig, M, Scott, C, Sebestian, S, Sehgal, S, Sem, V, Semenas, E, Serafini, E, Serchan, P, Shields, M, Shobha, R, Shosholcheva, M, Siamansour, T, Siddaiah, N, Siddiqi, K, Sinclair, R, Singh, P, Singh, R, Sinha, A, Skinner, A, Smee, E, Smekalova, O, Smith, N, Smith, T, Smitz, C, Smole, D, Sojcic, N, Soler Pedrola, M, Somanath, S, Sonksen, J, Sorella, M, Sormus, A, Soro, M, Soto, C, Spada, A, Spadaro, S, Spaeth, J, Sparr, H, Spielmann, A, Spindler-Vesel, A, Stamelos, M, Stancombe L, L, Stanculescu, A, Standl, T, Standley, T, Stanek, O, Stanisavljevic, S, Starczewska, M, Stauble, C, Steen, J, Stefan, O, Stell, E, Stera, C, Stevens, M, Stoerckel, M, Stosic, B, Stourac, P, Stroumpoulis, K, Struck, R, Suarez de la Rica, A, Sultanpori, A, Sundara Rajan, R, Suying, O, Svensen, C, Swan, L, Syrogianni, P, Sysiak, J, Szederjesi, J, Taddei, S, Tan Hao, E, Tanou, V, Tarabova, K, Tardaguila Sancho, P, Tarroso, M, Tartaglione, M, Taylor, E, Tbaily, L, Telford, R, Terenzoni, M, Theodoraki, K, Thornley, H, Tiganiuc, L, Toim, H, Tomescu, D, Tommasino, C, Toni, J, Toninelli, A, Toretti, I, Townley, S, Trepenaitis, D, Trethowan, B, Tsaousi, G, Tsiftsi, A, Tudor, A, Turan, G, Turhan, S, Unic-Stojanovic, D, Unterbuchner, C, Unzueta, C, Uranjek, J, Ursic, T, Vaida, S, Valldeperas Ferrer, S, Valldeperas Hernandez, M, Valsamidis, D, Van Beek, R, Van dasselaer, N, Van Der Beek, T, Van Duivenvoorde, Y, van Klei, W, Van Poorter, F, Van Zaane, B, Van Zundert, T, Van Zyl, R, Vargas Munoz, A, Varsani, N, Vasconcelos, P, Vassilakis, G, Vecchiatini, T, Vecera, L, Vercauteren, M, Verdouw, B, Verheyen, V, Verri, M, Vicari Sottosanti, L, Vico, M, Vidal Mitjans, P, Vilardi, A, Vissicchio, D, Vitale, G, Vitkovic, B, Vizcaychipi, M, Voicu, A, Voje, M, Volfova, I, Volta, C, Von Lutterotti, T, von Tiesenhausen, A, Vrecic-Slabe, S, Vukcevic, D, Vukovic, R, Vullo, P, Wade, A, Wallberg, H, Wallden, J, Wallner, J, Walther Sturesson, L, Watson, D, Weber, S, Wegiel Leskiewiq, A, Weller, D, Wensing, C, Werkmann, M, Westberg, H, Wikstrom, E, Williams, B, Wilson, R, Wirth, S, Wittmann, M, Wood, L, Wright, S, Zachoval, C, Zambon, M, Zampieri, S, Zampone, S, Zangrillo, A, Zani, G, Zavackiene, A, Zieglerder, R, Zonneveldt, H, Zsisku, L, Zucker, T, Zukowski, M, Zuleika, M, Zupaneie, D, Kirmeier E., Eriksson L. I., Lewald H., Jonsson Fagerlund M., Hoeft A., Hollmann M., Meistelman C., Hunter J. M., Ulm K., Blobner M., Abad Gurumeta A., Abernethy C., Abigail P., Achaibar K., Adam E., Afshari A., Agudelo Montoya M. E., Akgun F. N., Aletti G., Alkis N., Allan K., Allan A., Allaouchiche B., Allcock C., Almasy E., Amey I., Amigoni M., Andersen E., Andersson P., Anipchenko N., Antunes P., Armstrong E., Aslam T. N., Aslin B., Assuncao J. P., Ausserer J., Avvai M., Awad N., Ayas Montero B., Ayuso M., Azevedo P., Badarau V., Badescu R., Baiardo Redaelli M., Baird C., Baird Y., Baker T., Balaji P., Balan C., Balandin A., Balescu-Arion C., Baliuliene V., Baltasar Isabel J., Baluch S. N., Bandrabur D., Bankewitz C., Barber K., Barbera F., Barcraft-Barnes H., Barletti V., Barnett G., Baron K., Barros A., Barsan V., Bartlett P., Batistaki C., Baumgarten G., Baytas V., Beauchamp N., Becerra Cayetano I. A., Bell S., Bellandi M., Belletti A., Belmonte Cuenca J., Benitez-Cano A., Beretta L., Berger M., Bergmann N., Bergmark K., Bermudez Lopez M., Bernotaite M., Beurskens C., Bidd H., Bifulco F., Bignami E., Bilic A., Bilskiene D., Bischoff P., Bishop L., Bjonness T., Blaylock H., Blethyn K., Blincoe T., Blokhin I., Blunt N., Boer C., Bois G., Bonicolini E., Booth J., Borecka-Kedzierska M., Borstnar K., Borys M., Boselli E., Bouvet L., Bouwman A., Bowen L., Bowrey S., Boxall L., Bozic T., Bradley T., Branco T., Brazzi L., Brazzoni M., Brear T., Brogly N., Brohi F., Broms J., Bubliauskas A., Bucolo G. E., Buerkle H., Buggy D., Buhre W., Bukauskas T., Butturini F., Byttner A., Cabrera Diaz I., Calderon A., Calhau R., Callejo A., Cammu G., Campesato M., Can O. S., Candeias M., Cantor A., Carise E., Carmona C., Carreteiro J., Carrieri C., Carter A., Casal M., Casanova I., Cascella M., Casero L. M., Casiraghi G. M., Castelo-Branco L., Castro Arranz C., Cernea D. D., Cervantes J., Chandler B., Charnock R., Chatzimicali A., Chinery E., Chishti A., Chondhury P., Christie E., Christodoudiles G., Ciardo S., Cimpeanu L., Cindea I., Cinnella G., Clark S., Clayton M., Cocu S., Collyer T., Colvin C., Cope S., Copeta F., Copotoiu S. -M., Correia de Barros F., Corso R. M., Cortegiani A., Costa G., Cowton A., Cox N., Craig J., Cricca V., Cronin J., Cunha M., Cuomo A., Curley K., Czuczwar M., Dabrowska D., Damster S., Danguy des Deserts M., Daniliuc A., Danninger T., Darwish I., Dascalu C., Davies K., Davies S., De Boer H., De Flaviis A., De Selincourt G., Deana C., Debaene B., Debreceni G., Dedhia J., Delgado Garcia I., Della Rocca G., Delroy-Buelles L., Desai T., Dhillon P., Di Giacinto I., Di Mauro P., Diaz Gomez T. V., Dimitrovski A., Dinic V., Dirzu D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurnakova P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil J., Fernandez Castineira A., Fernandez Castineira J., Fernando A., Ferrando C., Ferreira L., Ferreira P., Feyling A., Filipescu D., Fleischer A., Floris L., Foerster U., Fox B., Franke U., Frasca D., Frey C., Frost V., Fullin G., Fumagalli J., Furneval J., Fusari M., Gallacher S., Galushka S., Gambale G., Gambino I., Garcia-Perez M. L., Garg S., Garlak J., Gavranovic Z., Gavrilov R., Gaynor L., Gecaj Gashi A., Georghiou M., Gerjevic B., Gferer G., Giarratano A., Gibson A., Gievski V., Giles J., Gillberg L., Gilowska K., Gilsanz Rodriguez F., Gioia A., Giovannoni C., Girotra V., Gkinas D., Gkiokas G., Godoroja D., Goebel U., Goel V., Gonzalez M., Goranovic T., Gornik-Wlaszczuk E., Gosavi S., Gottfridsson P., Gottschalk A., Granell M., Granstrom A., Grassetto A., Greenwood A., Grigoras I., Grintescu I., Gritsan A., Gritsan G., Grynyuk A., Guadagnin G. M., Guarnieri M., Guclu C., Guerrero Diez M., Gunenc F., Gunther U., Gupta P., Guttenthaler V., Hack Y., Hafisayena A., Hagau N., Haldar J., Hales D., Hanci V., Hanna-Jumma S., Harazim H., Harlet P., Harper D., Harris B., Harvey O., Hashimi M., Hawkins L., Hayes C., Heaton J., Heier T., Helliwell L., Hemmes S., Henderson K., Hermanides J., Hermanns H., Herrera Hueso B., Hestenes S., Hettiarachchi R., Highgate J., Hodgson K., Hoelbling D., Holland J., Horhota L., Hormis A., Hribar R., Hua A., Humphreys S., Humphries R., Humplikova S., Hunt J., Husnain A., Hussein A., Hyams B., Iannuccelli F., Ilette K., Ilyas C., Inan T., India I., Ionitav V., Irwin F., Jain V., Janez B., Jankovic R., Jenkins S., Jenko M., Jimenez R., Jimenez Gomez B., Joachim S., Joelsson-Alm E., John J., Jonikaite L., Jovic M., Jungwirth B., Junke E., Kabakov B., Kadaoui S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgassner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert A. W. M. M., Kopp K., Korfiotis D., Korolkov O., Kosinova M., Kostenberger M., Kotzinger O., Kovacevic M., Kranke P., Kranke E., Kraus C., Kraus S., Kubitzek C., Kucharski R., Kucukguclu S., Kudrashou A., Kumar V., Kummen L., Kunit C., Kushakovsky V., Kuvaki B., Kuzmanovska B., Kyttari A., Landoni G., Lau G., Lazarev K., Legett S., Legrottaglie A. M., Leonardi S., Leong M., Lercher H., Leuvrey M., Leva B., Levstek M., Limb J., Lindholm E., Linton F., Liperi C., Lipski F., Lirk P., Lisi A., Liskova K., Lluch Oltra A., Loganathan V., Lombardi S., Lopez E., Lopez Rodriguez M., Lorenzini L., Lowicka M., Lugovoy A., Luippold M., Lumb A., Macas A., Macgregor M., Machado H., Maciariello M., Madeira I., Maitan S., Majewski J., Maldini B., Malewski G., Manfredini L., Manner O., Marchand B., Marcu A., Margalef J., Margarson M., Marinheiro L., Markic A., Markovic Bozic J., Marrazzo F., Martin J., Martin Ayuso M., Martinez E., Martino E. A., Martinson V., Marusic-Gaser K., Mascarenhas C., Mathis C., Matsota P., Mavrommati E., Mazul Sunko B., McCourt K., McGill N., McKee R., Meco B. C., Meier S., Melbourne S., Melbybrathen G., Meli A., Melia A., Melotti R. M., Menga M. R., Mercer P., Merotra S., Mescolini S., Metterlein T., Michalov M., Michlig S., Midgley S., Milic M., Milojevic M., Minana A., Minto G., Mirabella L., Mirea L., Mittelstadt L., Moeglen A., Moise A., Mokini Z., Molin A., Molto L., Monea M. C., Montalto F., Montgomery J., Montgomery C., Montillo G., Moore S., Moore F., Moreira Z., Moreno T., Moreno R., Moret E., Moreton S., Morgan M., Moro Velasco C., Morri D., Moull A., Moura F., Mraz P., Mrozek K., Mukhtar K., Muniyappa S., Murray H., Murthy B. V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. I., Reavley C., Reid J., Reschreiter H., Rial E., Ribas Carrasco P., Ribeiro S., Rich N., Richardson L., Rimaitis K., Rimaitis M., Ringvold E. -M., Ripke F., Ristescu I., Ritchie K., Rodenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sa J., Sa Couto P., Saby S., Sagic J., Saleh O., Sales G., Sanchez Sanchez Y., Sanghera S., Sanli Karip C., Santiveri Papiol F. J., Santos S., Sarno S., Saul D., Saunders D., Savic N., Scalco L., Scanlon D., Schaller S., Schax C., Scheffer G. J., Schening A., Schiavone V., Schmidt-Ehrenberg F., Schmidt-Mutter C., Schonberg C., Schopflin C., Schreiber J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojcic N., Soler Pedrola M., Somanath S., Sonksen J., Sorella M. C., Sormus A., Soro M., Soto C., Spada A., Spadaro S., Spaeth J., Sparr H., Spielmann A., Spindler-Vesel A., Stamelos M., Stancombe L L., Stanculescu A., Standl T., Standley T., Stanek O., Stanisavljevic S., Starczewska M., Stauble C., Steen J., Stefan O. M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., and Zupaneie D.
Abstract: Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary
Published: 2019

9. Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis

Author: Ahn, R, Vukcevic, D, Motyer, A, Nititham, J, Squire, DM, Hollenbach, JA, Norman, PJ, Ellinghaus, E, Nair, RP, Tsoi, LC, Oksenberg, J, Foerster, J, Lieb, W, Weidinger, S, Franke, A, Elder, JT, Jorgenson, E, Leslie, S, Liao, W, Ahn, R, Vukcevic, D, Motyer, A, Nititham, J, Squire, DM, Hollenbach, JA, Norman, PJ, Ellinghaus, E, Nair, RP, Tsoi, LC, Oksenberg, J, Foerster, J, Lieb, W, Weidinger, S, Franke, A, Elder, JT, Jorgenson, E, Leslie, S, and Liao, W
Abstract: Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis.
Published: 2021

10. Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept

Author: Hamshere, M. L., Green, E. K., Jones, I. R., Jones, L., Moskvina, V., Kirov, G., Grozeva, D., Nikolov, I., Vukcevic, D., Caesar, S., Gordon-Smith, K., Fraser, C., Russell, E., Breen, G., St Clair, D., Collier, D. A., Young, A. H., Ferrier, I. N., Farmer, A., McGuffin, P., Holmans, P. A., Owen, M. J., OʼDonovan, M. C., and Craddock, N.
Published: 2009

11. Epistatic interactions between killer immunoglobulin-like receptors and human leukocyte antigen ligands are associated with ankylosing spondylitis

Author: Roopenian, DC, Hanson, AL, Vukcevic, D, Leslie, S, Harris, J, Cao, K-AL, Kenna, TJ, Brown, MA, Roopenian, DC, Hanson, AL, Vukcevic, D, Leslie, S, Harris, J, Cao, K-AL, Kenna, TJ, and Brown, MA
Abstract: The killer immunoglobulin-like receptors (KIRs), found predominantly on the surface of natural killer (NK) cells and some T-cells, are a collection of highly polymorphic activating and inhibitory receptors with variable specificity for class I human leukocyte antigen (HLA) ligands. Fifteen KIR genes are inherited in haplotypes of diverse gene content across the human population, and the repertoire of independently inherited KIR and HLA alleles is known to alter risk for immune-mediated and infectious disease by shifting the threshold of lymphocyte activation. We have conducted the largest disease-association study of KIR-HLA epistasis to date, enabled by the imputation of KIR gene and HLA allele dosages from genotype data for 12,214 healthy controls and 8,107 individuals with the HLA-B*27-associated immune-mediated arthritis, ankylosing spondylitis (AS). We identified epistatic interactions between KIR genes and their ligands (at both HLA subtype and allele resolution) that increase risk of disease, replicating analyses in a semi-independent cohort of 3,497 cases and 14,844 controls. We further confirmed that the strong AS-association with a pathogenic variant in the endoplasmic reticulum aminopeptidase gene ERAP1, known to alter the HLA-B*27 presented peptidome, is not modified by carriage of the canonical HLA-B receptor KIR3DL1/S1. Overall, our data suggests that AS risk is modified by the complement of KIRs and HLA ligands inherited, beyond the influence of HLA-B*27 alone, which collectively alter the proinflammatory capacity of KIR-expressing lymphocytes to contribute to disease immunopathogenesis.
Published: 2020

12. Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Author: Iglesias, AI, Mishra, A, Vitart, V, Bykhovskaya, Y, Hoehn, R, Springelkamp, H, Cuellar-Partida, G, Gharahkhani, P, Bailey, JNC, Willoughby, CE, Li, X, Yazar, S, Nag, A, Khawaja, AP, Polasek, O, Siscovick, D, Mitchell, P, Tham, YC, Haines, JL, Kearns, LS, Hayward, C, Shi, Y, van Leeuwen, EM, Taylor, KD, Bonnemaijer, P, Rotter, JI, Martin, NG, Zeller, T, Mills, RA, Souzeau, E, Staffieri, SE, Jonas, JB, Schmidtmann, I, Boutin, T, Kang, JH, Lucas, SEM, Wong, TY, Beutel, ME, Wilson, JF, Uitterlinden, AG, Vithana, EN, Foster, PJ, Hysi, PG, Hewitt, AW, Khor, CC, Pasquale, LR, Montgomery, GW, Klaver, CCW, Aung, T, Pfeiffer, N, Mackey, DA, Hammond, CJ, Cheng, C-Y, Craig, JE, Rabinowitz, YS, Wiggs, JL, Burdon, KP, van Duijn, CM, MacGregor, S, Wang, JJ, Rochtchina, E, Attia, J, Scott, R, Holliday, EG, Baird, PN, Xie, J, Inouye, M, Viswanathan, A, Sim, X, Allingham, RR, Brilliant, MH, Budenz, DL, Christen, WG, Fingert, J, Friedman, DS, Gaasterland, D, Gaasterland, T, Hauser, MA, Kraft, P, Lee, RK, Lichter, PR, Liu, Y, Loomis, SJ, Moroi, SE, Pericak-Vance, MA, Realini, A, Richards, JE, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Vollrath, D, Weinreb, RN, Wollstein, G, Zack, DJ, Zhang, K, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Grp, BMES-G, Consortium, N, and Control, WTC
Subjects: Lumican, genetic structures, Fibrillin-1, General Physics and Astronomy, Gene Expression, Q1, Corneal Diseases, Marfan Syndrome, Cornea, ADAMTS Proteins, Myopia, Link (knot theory), lcsh:Science, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Corneal Dystrophies, Hereditary, Multidisciplinary, Eye Diseases, Hereditary, symbols, NEIGHBORHOOD consortium, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Proteoglycans, Decorin, Glaucoma, Open-Angle, Science, Quantitative Trait Loci, Computational biology, Biology, Keratoconus, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, White People, Article, symbols.namesake, Transforming Growth Factor beta2, Quantitative Trait, Heritable, Asian People, Genome-Wide Association Analysis, Humans, Author Correction, Eye Disease and Disorders of Vision, Loeys-Dietz Syndrome, Genome, Human, Wellcome Trust Case Control Consortium 2, Blue Mountains Eye Study - GWAS group, General Chemistry, Mendelian Randomization Analysis, R1, eye diseases, Mendelian inheritance, Ehlers-Danlos Syndrome, lcsh:Q, sense organs, Genome-Wide Association Study
Abstract: Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = −0.62, P = 5.30 × 10−5) but not between CCT and primary open-angle glaucoma (r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation., Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.
Published: 2019
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13. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Author: Lyons, P.A., Peters, J.E., Alberici, F., Liley, J., Coulson, R.M.R., Astle, W., Baldini, C., Bonatti, F., Cid, M.C., Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D.R.W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M.A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G.A., Rewerska, B., Schett, G., Sinico, R.A., Szczeklik, W., Tesar, V., Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A.S., Bruce, I., Clarkson, M., Conlon, N., DasGupta, B., Doulton, T.W.R., Espígol-Frigolé, Georgina, Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernández Rodríguez, José, Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A.A., Marguerie, C., Maritati, F., Marvisi, C., McHugh, N.J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, L., Pesci, A., Prieto-Gonzalez, S., Ramentol-Sintas, Marc, Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans-Laque, R., Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R.A., Vaglio, A., Holle, J.U., Wallace, C., Smith, K.G.C., and Universitat Autònoma de Barcelona
Subjects: Eosinophils, Genetic Loci, Granulomatosis with Polyangiitis, Humans, Genetic Predisposition to Disease, Mendelian Randomization Analysis, Genetic Association Studies, Antibodies, Antineutrophil Cytoplasmic, Genome-Wide Association Study
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
Published: 2019

14. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Author: Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, Lyons, PA, Peters, JE, Cid, MC, Little, MA, Ramierez, GA, Butterworth, AS, DasGupta, B, Doulton, TWR, Manfredi, AA, McHugh, NJ, Watts, RA, Holle, JU, Smith, KGC, Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, Lyons, PA, Peters, JE, Cid, MC, Little, MA, Ramierez, GA, Butterworth, AS, DasGupta, B, Doulton, TWR, Manfredi, AA, McHugh, NJ, Watts, RA, Holle, JU, and Smith, KGC
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
Published: 2019

15. Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Author: Harold, D, Connolly, S, Riley, BP, Kendler, KS, McCarthy, SE, McCombie, WR, Richards, A, Owen, MJ, O'Donovan, MC, Walters, J, Donnelly, P, Bates, L, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Hopkins, L, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Ripke, S, Neale, BM, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M-L, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chan, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Lee, J, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Muller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Buxbaum, JD, Borglum, AD, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, Harold, D, Connolly, S, Riley, BP, Kendler, KS, McCarthy, SE, McCombie, WR, Richards, A, Owen, MJ, O'Donovan, MC, Walters, J, Donnelly, P, Bates, L, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Hopkins, L, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Ripke, S, Neale, BM, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M-L, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chan, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Lee, J, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Muller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Buxbaum, JD, Borglum, AD, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, and Sullivan, PF
Abstract: Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.
Published: 2019

16. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Author: Lyons, PA, Peters, JE, Alberici, F, Liley, J, Coulson, RMR, Astle, W, Baldini, C, Bonatti, F, Cid, MC, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, DRW, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, MA, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramirez, GA, Rewerska, B, Schett, G, Sinico, RA, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, AS, Bruce, I, Clarkson, M, Conlon, N, DasGupta, B, Doulton, TWR, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, AA, Marguerie, C, Maritati, F, Marvisi, C, McHugh, NJ, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, RA, Vaglio, A, Holle, JU, Wallace, C, Smith, KGC, Lyons, PA, Peters, JE, Alberici, F, Liley, J, Coulson, RMR, Astle, W, Baldini, C, Bonatti, F, Cid, MC, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, DRW, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, MA, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramirez, GA, Rewerska, B, Schett, G, Sinico, RA, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, AS, Bruce, I, Clarkson, M, Conlon, N, DasGupta, B, Doulton, TWR, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, AA, Marguerie, C, Maritati, F, Marvisi, C, McHugh, NJ, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, RA, Vaglio, A, Holle, JU, Wallace, C, and Smith, KGC
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
Published: 2019

17. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases (vol 9, 1864, 2018)

Author: Iglesias, AI, Mishra, A, Vitart, V, Bykhovskaya, Y, Hoehn, R, Springelkamp, H, Cuellar-Partida, G, Gharahkhani, P, Bailey, JNC, Willoughby, CE, Li, X, Yazar, S, Nag, A, Khawaja, AP, Polasek, O, Siscovick, D, Mitchell, P, Tham, YC, Haines, JL, Kearns, LS, Hayward, C, Shi, Y, van Leeuwen, EM, Taylor, KD, Bonnemaijer, P, Rotter, JI, Martin, NG, Zeller, T, Mills, RA, Souzeau, E, Staffieri, SE, Jonas, JB, Schmidtmann, I, Boutin, T, Kang, JH, Lucas, SEM, Wong, TY, Beutel, ME, Wilson, JF, Uitterlinden, AG, Vithana, EN, Foster, PJ, Hysi, PG, Hewitt, AW, Khor, CC, Pasquale, LR, Montgomery, GW, Klaver, CCW, Aung, T, Pfeiffer, N, Mackey, DA, Hammond, CJ, Cheng, C-Y, Craig, JE, Rabinowitz, YS, Wiggs, JL, Burdon, KP, van Duijn, CM, MacGregor, S, Wang, JJ, Rochtchina, E, Attia, J, Scott, R, Holliday, EG, Baird, PN, Xie, J, Inouye, M, Viswanathan, A, Sim, X, Allingham, RR, Brilliant, MH, Budenz, DL, Christen, WG, Fingert, J, Friedman, DS, Gaasterland, D, Gaasterland, T, Hauser, MA, Kraft, P, Lee, RK, Lichter, PR, Liu, Y, Loomis, SJ, Moroi, SE, Pericak-Vance, MA, Realini, A, Richards, JE, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Vollrath, D, Weinreb, RN, Wollstein, G, Zack, DJ, Zhang, K, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Iglesias, AI, Mishra, A, Vitart, V, Bykhovskaya, Y, Hoehn, R, Springelkamp, H, Cuellar-Partida, G, Gharahkhani, P, Bailey, JNC, Willoughby, CE, Li, X, Yazar, S, Nag, A, Khawaja, AP, Polasek, O, Siscovick, D, Mitchell, P, Tham, YC, Haines, JL, Kearns, LS, Hayward, C, Shi, Y, van Leeuwen, EM, Taylor, KD, Bonnemaijer, P, Rotter, JI, Martin, NG, Zeller, T, Mills, RA, Souzeau, E, Staffieri, SE, Jonas, JB, Schmidtmann, I, Boutin, T, Kang, JH, Lucas, SEM, Wong, TY, Beutel, ME, Wilson, JF, Uitterlinden, AG, Vithana, EN, Foster, PJ, Hysi, PG, Hewitt, AW, Khor, CC, Pasquale, LR, Montgomery, GW, Klaver, CCW, Aung, T, Pfeiffer, N, Mackey, DA, Hammond, CJ, Cheng, C-Y, Craig, JE, Rabinowitz, YS, Wiggs, JL, Burdon, KP, van Duijn, CM, MacGregor, S, Wang, JJ, Rochtchina, E, Attia, J, Scott, R, Holliday, EG, Baird, PN, Xie, J, Inouye, M, Viswanathan, A, Sim, X, Allingham, RR, Brilliant, MH, Budenz, DL, Christen, WG, Fingert, J, Friedman, DS, Gaasterland, D, Gaasterland, T, Hauser, MA, Kraft, P, Lee, RK, Lichter, PR, Liu, Y, Loomis, SJ, Moroi, SE, Pericak-Vance, MA, Realini, A, Richards, JE, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Vollrath, D, Weinreb, RN, Wollstein, G, Zack, DJ, Zhang, K, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, and Whittaker, P
Abstract: Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.
Published: 2019

18. Temporal clustering of rotational glitches in the Crab pulsar

Author: Carlin, J B, primary, Melatos, A, additional, and Vukcevic, D, additional
Published: 2018
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19. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Author: Iglesias, A.I. (Adriana I.), Mishra, A. (Aniket), Vitart, V. (Veronique), Bykhovskaya, Y. (Yelena), Höhn, R. (René), Springelkamp, H. (Henriët), Cuellar-Partida, G. (Gabriel), Gharahkhani, P. (Puya), Bailey, J.N.C. (Jessica N. Cooke), Willoughby, C.E. (Colin E.), Li, X. (Xiaohui), Yazar, S. (Seyhan), Nag, A. (Abhishek), Khawaja, A.P. (Anthony), Polasek, O. (Ozren), Siscovick, D.S. (David), Mitchell, P. (Paul), Tham, Y.C. (Yih Chung), Haines, J.L. (Jonathan), Kearns, L.S. (Lisa S.), Hayward, C. (Caroline), Shi, Y. (Yuan), Van Leeuwen, E.M. (Elisabeth M.), Taylor, K.D. (Kent), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A. (Ananth), Sim, X. (Xueling), Bonnemaijer, P.W.M. (Pieter), Rotter, J.I. (Jerome I.), Martin, N.G. (Nicholas G.), Zeller, T. (Tanja), Mills, R.A. (Richard), Staffieri, S.E. (Sandra E.), Jonas, J.B. (Jost B.), Schmidtmann, I. (Irene), Boutin, T. (Thibaud), Kang, J.H. (Jae H.), Lucas, S.E.M. (Sionne E.M.), Wong, T.Y. (Tien Yin), Beutel, M.E. (Manfred E.), Wilson, J.F. (James F.), Allingham, R.R. (R Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Christen, W.G. (William G.), Fingert, J. (John), Friedman, D.S. (David), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Hauser, M.A. (Michael), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Loomis, S.J. (Stephanie J.), Moroi, S.E. (Sayoko), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Richards, J.E. (Julia E.), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Zack, D.J. (Donald), Zhang, K. (Kang), Donnelly, P. (Peter), Barroso, I.E. (Inês), Blackwell, J.M. (Jenefer M.), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panos), Duncanson, A. (Audrey), Jankowski, J. (Janusz), Markus, H.S. (Hugh), Mathew, J. (Joseph), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Wood, N.W. (Nicholas W.), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Langford, C. (Cordelia), Hunt, S.E. (Sarah E.), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, P. (Patrick), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Uitterlinden, A.G. (André), Vithana, E.N. (Eranga), Foster, P.J. (Paul), Hysi, P.G. (Pirro), Hewitt, A.W. (Alex W.), Khor, C.C., Pasquale, L.R. (Louis), Montgomery, G.W. (Grant W.), Klaver, C.C.W. (Caroline), Aung, T. (Tin), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Hammond, C.J. (Christopher), Cheng, C.-Y. (Ching-Yu), Craig, J.E. (Jamie), Rabinowitz, Y.S. (Yaron), Wiggs, J.L. (Janey L.), Burdon, K.P. (Kathryn), Duijn, C.M. (Cornelia) van, MacGregor, S. (Stuart), Iglesias, A.I. (Adriana I.), Mishra, A. (Aniket), Vitart, V. (Veronique), Bykhovskaya, Y. (Yelena), Höhn, R. (René), Springelkamp, H. (Henriët), Cuellar-Partida, G. (Gabriel), Gharahkhani, P. (Puya), Bailey, J.N.C. (Jessica N. Cooke), Willoughby, C.E. (Colin E.), Li, X. (Xiaohui), Yazar, S. (Seyhan), Nag, A. (Abhishek), Khawaja, A.P. (Anthony), Polasek, O. (Ozren), Siscovick, D.S. (David), Mitchell, P. (Paul), Tham, Y.C. (Yih Chung), Haines, J.L. (Jonathan), Kearns, L.S. (Lisa S.), Hayward, C. (Caroline), Shi, Y. (Yuan), Van Leeuwen, E.M. (Elisabeth M.), Taylor, K.D. (Kent), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A. (Ananth), Sim, X. (Xueling), Bonnemaijer, P.W.M. (Pieter), Rotter, J.I. (Jerome I.), Martin, N.G. (Nicholas G.), Zeller, T. (Tanja), Mills, R.A. (Richard), Staffieri, S.E. (Sandra E.), Jonas, J.B. (Jost B.), Schmidtmann, I. (Irene), Boutin, T. (Thibaud), Kang, J.H. (Jae H.), Lucas, S.E.M. (Sionne E.M.), Wong, T.Y. (Tien Yin), Beutel, M.E. (Manfred E.), Wilson, J.F. (James F.), Allingham, R.R. (R Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Christen, W.G. (William G.), Fingert, J. (John), Friedman, D.S. (David), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Hauser, M.A. (Michael), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Loomis, S.J. (Stephanie J.), Moroi, S.E. (Sayoko), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Richards, J.E. (Julia E.), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Zack, D.J. (Donald), Zhang, K. (Kang), Donnelly, P. (Peter), Barroso, I.E. (Inês), Blackwell, J.M. (Jenefer M.), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panos), Duncanson, A. (Audrey), Jankowski, J. (Janusz), Markus, H.S. (Hugh), Mathew, J. (Joseph), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Wood, N.W. (Nicholas W.), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Langford, C. (Cordelia), Hunt, S.E. (Sarah E.), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, P. (Patrick), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Uitterlinden, A.G. (André), Vithana, E.N. (Eranga), Foster, P.J. (Paul), Hysi, P.G. (Pirro), Hewitt, A.W. (Alex W.), Khor, C.C., Pasquale, L.R. (Louis), Montgomery, G.W. (Grant W.), Klaver, C.C.W. (Caroline), Aung, T. (Tin), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Hammond, C.J. (Christopher), Cheng, C.-Y. (Ching-Yu), Craig, J.E. (Jamie), Rabinowitz, Y.S. (Yaron), Wiggs, J.L. (Janey L.), Burdon, K.P. (Kathryn), Duijn, C.M. (Cornelia) van, and MacGregor, S. (Stuart)
Abstract: Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.
Published: 2018
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20. The UK Biobank resource with deep phenotyping and genomic data

Author: Bycroft, C, Freeman, C, Petkova, D, Band, G, Elliott, LT, Sharp, K, Motyer, A, Vukcevic, D, Delaneau, O, O'Connell, J, Cortes, A, Welsh, S, Young, A, Effingham, M, McVean, G, Leslie, S, Allen, N, Donnelly, P, Marchini, J, Bycroft, C, Freeman, C, Petkova, D, Band, G, Elliott, LT, Sharp, K, Motyer, A, Vukcevic, D, Delaneau, O, O'Connell, J, Cortes, A, Welsh, S, Young, A, Effingham, M, McVean, G, Leslie, S, Allen, N, Donnelly, P, and Marchini, J
Abstract: The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
Published: 2018

21. Bayesian modelling of lung function data from multiple-breath washout tests

Author: Mahar, RK, Carlin, JB, Ranganathan, S, Ponsonby, A-L, Vuillermin, P, Vukcevic, D, Mahar, RK, Carlin, JB, Ranganathan, S, Ponsonby, A-L, Vuillermin, P, and Vukcevic, D
Abstract: Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 individuals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions.
Published: 2018

22. Erratum: Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype

Author: Craddock, N, Jones, L, Jones, I R, Kirov, G, Green, E K, Grozeva, D, Moskvina, V, Nikolov, I, Hamshere, M L, Vukcevic, D, Caesar, S, Gordon-Smith, K, Fraser, C, Russell, E, Norton, N, Breen, G, St Clair, D, Collier, D A, Young, A H, Ferrier, I N, Farmer, A, McGuffin, P, Holmans, P A, Donnelly, P, Owen, M J, and O'Donovan, M C
Published: 2010
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23. Genome-Wide Association Study Implicates HLA-C*01:02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

Author: Strange, A, Riley, BP, Spencer, CCA, Morris, DW, Pirinen, M, O'Dushlaine, CT, Su, Z, Maher, BS, Freeman, C, Cormican, P, Bellenguez, C, Kenny, EM, Band, G, Wormley, B, Donohoe, G, Dilthey, A, Moutsianas, L, Quinn, E, Edkins, S, Judge, R, Coleman, K, Hunt, S, Tropea, D, Roche, S, Cummings, L, Kelleher, E, McKeon, P, Dinan, T, McDonald, C, Murphy, KC, O'Callaghan, E, O'Neill, FA, Waddington, JL, Walsh, D, Giannoulatou, E, Langford, C, Deloukas, P, Gray, E, Dronov, S, Potter, S, Pearson, R, Vukcevic, D, Tashakkori-Ghanbaria, A, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Stone, J, Scolnick, E, Purcell, S, Sklar, P, Ripke, S, Walters, J, Owen, MJ, O'Donovan, MC, Peltonen, L, McVean, G, Kendler, KS, Gill, M, Donnelly, P, Corvin, A, Conso, ISG, Consortium, SGENE, Psychiat, SWG, and Consor, WTCC
Subjects: Adult, Male, Genotype, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Human leukocyte antigen, HLA-C Antigens, Major histocompatibility complex, Polymorphism, Single Nucleotide, Article, HLA-C, Calcium Channels, T-Type, Young Adult, Risk Factors, Databases, Genetic, tourette-syndrome, SNP, Humans, genetics, Genetic Predisposition to Disease, Allele, gene, Biological Psychiatry, Aged, Genetics, cacna1i, breakpoint, Aged, 80 and over, biology, deletions, polygene score, classical hla alleles, Middle Aged, hlac, major histocompatibility complex, disruption, biology.protein, Schizophrenia, Female, immp2l, Ireland, Genome-Wide Association Study
Abstract: BACKGROUND: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. METHODS: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10(-9) and in combined samples (rs2523722 p combined = 2.88 × 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. CONCLUSIONS: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.
Published: 2016

24. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

Author: Burton, PR, Clayton, DG, Cardon, LR, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Samani, NJ, Todd, JA, Donnelly, P, Barrett, JC, Davison, D, Easton, D, Evans, DM, Leung, HT, Marchini, JL, Morris, AP, Spencer, CC, Tobin, MD, Attwood, AP, Boorman, JP, Cant, B, Everson, U, Hussey, JM, Jolley, JD, Knight, AS, Koch, K, Meech, E, Nutland, S, Prowse, CV, Stevens, HE, Taylor, NC, Walters, GR, Walker, NM, Watkins, NA, Winzer, T, Jones, RW, McArdle, WL, Ring, SM, Strachan, DP, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskivina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGuffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, TD, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Thompson, JR, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Forbes, A, Lewis, CM, Onnie, CM, Prescott, NJ, Sanderson, J, Matthew, CG, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Webster, J, Brown, MJ, Lathrop, MG, Connell, J, Dominiczak, A, Marcano, CA, Burke, B, Dobson, R, Gungadoo, J, Lee, KL, Munroe, PB, Newhouse, SJ, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hilder, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DP, Thomson, W, Worthington, J, Dunger, DB, Widmer, B, Frayling, TM, Freathy, RM, Lango, H, Perry, JR, Shields, BM, Weedon, MN, Hattersley, AT, Hitman, GA, Walker, M, Elliott, KS, Groves, CJ, Lindgren, CM, Rayner, NW, Timpson, NJ, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, AV, Bradbury, LA, Farrar, C, Pointon, JJ, Wordsworth, P, Brown, MA, Franklyn, JA, Heward, JM, Simmonds, MJ, Gough, SC, Seal, S, Stratton, MR, Rahman, N, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Conway, D, Jallow, M, Rockett, KA, Bumpstead, SJ, Chaney, A, Downes, K, Ghori, MJ, Gwilliam, R, Hunt, SE, Inouye, M, Keniry, A, King, E, McGinnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdo'ttir, IB, Howie, BN, Su, Z, Teo, YY, Vukcevic, D, Bentley, D, Mitchell, SL, Newby, PR, Brand, OJ, Carr-Smith, J, Pearce, SH, Reveille, JD, Zhou, X, Sims, AM, Dowling, A, Taylor, J, Doan, T, Davis, JC, Savage, L, Ward, MM, Learch, TL, Weisman, MH, and Brown, M
Subjects: Linkage disequilibrium, Multiple Sclerosis, Genotype, Population, Single-nucleotide polymorphism, Genome-wide association study, Autoimmunity, Breast Neoplasms, Biology, medicine.disease_cause, Aminopeptidases, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Minor Histocompatibility Antigens, Genetics, medicine, Humans, Spondylitis, Ankylosing, Receptors, Immunologic, education, Genetic association, education.field_of_study, Ankylosing spondylitis, Thyroiditis, Autoimmune, Chromosome Mapping, Receptors, Interleukin, medicine.disease, Endoplasmic reticulum aminopeptidase 2, Genetics, Population, Haplotypes, Case-Control Studies, Immunology, North America
Abstract: We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
Published: 2016
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25. Genome-wide and fine-resolution association analysis of malaria in West Africa

Author: Muminatou, Jallow, Yik Ying Teo, Small, Kerrin S., Rockett, Kirk A., Panos, Deloukas, Clark, Taane G., Katja, Kivinen, Bojang, Kalifa A., Conway, David J., Margaret, Pinder, Giorgio, Sirugo, Fatou Sisay Joof, Stanley, Usen, Sarah, Auburn, Bumpstead, Suzannah J., Susana, Campino, Alison, Coffey, Andrew, Dunham, Fry, Andrew E., Angela, Green, Rhian, Gwilliam, Hunt, Sarah E., Michael, Inouye, Jeffreys, Anna E., Alieu, Mendy, Aarno, Palotie, Simon, Potter, Jiannis, Ragoussis, Jane, Rogers, Kate, Rowlands, Elilan, Somaskantharajah, Pamela, Whittaker, Claire, Widden, Peter, Donnelly, Bryan, Howie, Jonathan, Marchini, Andrew, Morris, Miguel, Sanjoaquin, Eric Akum Achidi, Tsiri, Agbenyega, Angela, Allen, Olukemi, Amodu, Patrick, Corran, Abdoulaye, Djimde, Amagana, Dolo, Doumbo, Ogobara K., Chris, Drakeley, Sarah, Dunstan, Jennifer, Evans, Jeremy, Farrar, Hien Tt, Fernando D., Horstmann, R. D., Ibrahim, M., Karunaweera, N., Kokwaro, G., Koram, K. A., Lemnge, M., Makani, J., Marsh, K., Michon, P., David, Modiano, Molyneux, M. E., Mueller, I., Parker, M., Peshu, N., Plowe, C. V., Puijalon, O., Reeder, J., Reyburn, H., Riley, E. M., Sakuntabhai, A., Singhasivanon, P., Sirima, S., Tall, A., Taylor, T. E., Thera, M., Troye Blomberg, M., Williams, T. N., Wilson, M., Wellcome Trust Case Control Consortium Kwiatkowski, D. P., Epidemiology Network: Achidi, Malaria Genomic E. A., Agbenyega, T., Ahmad, T., Alcock, D., Allen, S., Amenga Etego, L., Amodu, O., Apinjoh, T. O., Attwood, A. P., Auburn, S., Ball, S. G., Balmforth, A. J., Ban, M., Barbour, J., Barnwell, D., Barrett, J. C., Barrett, J. H., Barton, A., Bentley, D., Bishop, D. T., Bojang, K., Boorman, J. P., Bougouma, E., Bradbury, L. A., Braga Marcano, C. A., Braund, P. S., Bredin, F., Breen, G., Brown, M. A., Brown, M. J., Bruce, I. N., Bryan, C., Bull, S., Bumpstead, S. J., Burke, B., Burton, P. R., Caesar, S., Campino, S., Cant, B., Cardin, N. J., Cardon, L. R., Carucci, D., Caulfield, M., Chaney, A., Clark, T., Clayton, D. G., Collier, D. A., Compston, A., Compston, D. A., Connell, J., Conway, D., Cook, K., Corran, P., Craddock, N., Cummings, F. R., Davison, D., Deloukas, P., Devries, J., Dewasurendra, R., Diakite, M., Dixon, R. J., Djimde, A., Dobson, R., Dolo, A., Dominiczak, A., Donnelly, P., Donovan, H., Doumbo, O., Downes, K., Doyle, A., Drakeley, C., Drummond, H., Duffy, P., Duncanson, A., Dunger, D. B., Dunstan, S., Duombo, O., Easton, D., Elkin, A., Elliott, K. S., Elzein, A., Enimil, A., Evans, D., Evans, J., Everson, U., Eyre, S., Farmer, A., Farrall, M., Farrar, C., Farrar, J., Fernando, D., Ferreira, T., Ferrier, I. N., Fisher, S. A., Fitzpatrick, K., Forbes, A., Franklyn, J. A., Fraser, C., Frayling, T. M., Freathy, R. M., Ghansah, A., Ghori, J., Gilbert, P. D., Gordon Smith, K., Goris, A., Gottlieb, M., Gough, S. C., Green, A., Green, E. K., Groves, C. J., Grozeva, D., Gungadoo, J., Gwilliam, R., Hall, A. S., Hallgrimsdóttir, I. B., Hamshere, M. L., Hart, L., Hattersley, A. T., Heward, J. M., Hider, S. L., Tran Tinh Hien, Hill, A. V., Hilton, E., Hinks, A. M., Hitman, G. A., Holmans, P. A., Horstmann, Rolf D., Howie, B. N., Hubbart, C., Hughes, C., Hunt, S. E., Hussein, A., Hussey, J. M., Muntaser, Ibrahim, Iles, M. M., Inouye, M., Ishengoma, D., Jallow, M., Jeffreys, A. E., Jewell, D. P., John, Sl, Jolley, J. D., Jones, I. R., Jones, L., Jones, R. W., Nadira, Karunaweera, Keniry, A., King, E., Kirov, G., Kivinen, K., Knight, A. S., Koch, K., Gilbert, Kokwaro, Koram, Kwadwo A., Lango, H., Lathrop, G. M., Lee, K. L., Lees, C. W., Martha, Lemnge, Leung, H. T., Lewis, C. M., Lin, E., Lindgren, C. M., Ly, A., Macinnis, B., Julie, Makani, Mangano, Valentina, Mangino, M., Manjurano, A., Manning, L., Mansfield, J. C., Manske, M., Maqbool, A., Marchini, J. L., Kevin, Marsh, Maslen, G., Mathew, C. G., Mcardle, W. L., Mccarthy, M. I., Mccreight, M., Mcginnis, R., Mcguffin, P., Meech, E., Mendy, A., Pascal, Michon, Mohiuddin, M. K., Molyneux, Malcolm E., Morris, A. P., Moskvina, V., Moyes, C., Ivo, Mueller, Munroe, P. B., Mutabingwa, T., Ndila, C. M., Newhouse, S. J., Newport, M., Nikolov, I., Nimmo, E. R., Nutland, S., Nyirongo, V., O'Donovan, M. C., Oluoch, T., Onipinla, A., Onnie, C. M., Ouwehand, W. H., Owen, M. J., Michael, Parker, Parkes, M., Pembrey, M., Pereira Gale, J., Perry, J. R., Norbert, Peshu, Plowe, Christopher V., Pointon, J. J., Potter, C., Potter, S., Prescott, N. J., Prowse, C. V., Odile, Puijalon, Quyen, N. T., Ragoussis, J., Rahman, N., Ravindrarajah, R., Rayner, N. W., John, Reeder, Hugh, Reyburn, Riley, Eleanor M., Ring, S. M., Risley, P., Rockett, K. A., Rogers, J., Rowlands, K., Anavaj, Sakuntabhai, Samani, N. J., Sanderson, J., Sanjoaquin, M., Satsangi, J., Sawcer, S. J., Seal, S., Shields, B. M., Silman, A. J., Simmonds, M. J., Pratap, Singhasivanon, Sodiomon, Sirima, Sirugo, G., Small, K. S., Somaskantharajah, E., Spencer, C. C., St Clair, D., Stevens, H. E., Stevens, M., Stevens, S., Strachan, D. P., Stratton, M. R., Su, Z., Suriyaphol, P., Symmons, D. P., Adama, Tall, Taylor, N. C., Taylor, Terrie E., Teo, Y., Teo, Y. Y., Mahamadou, Thera, Thompson, J. R., Thomson, W., Timpson, N. J., Tobin, M. D., Todd, J. A., Todhunter, C. E., Toure, O., Tremelling, M., Marita Troye Blomberg, Vanderwal, A., Vukcevic, D., Walker, M., Walker, N. M., Wallace, C., Walters, G. R., Walton, R., Watkins, N. A., Watson, R., Webster, J., Weedon, M. N., Whittaker, P., Widmer, B., Williams, Thomas N., Williamson, R., Michael, Wilson, Winzer, T., Withers, D., Wordsworth, P., Worthington, J., Wrigley, R., Xue, M., Young, A. H., Yuldasheva, N., and Zeggini, E.
Subjects: Linkage disequilibrium, Hemoglobin, Sickle, Population, Genome-wide association study, Locus (genetics), Biology, Population stratification, Polymorphism, Single Nucleotide, Severity of Illness Index, Linkage Disequilibrium, Article, Gene mapping, Reference Values, Ethnicity, Genetics, Humans, education, Genetic association, education.field_of_study, Polymorphism, Genetic, Chromosome Mapping, Genetic Variation, Malaria, Gambia, Imputation (genetics), Genome-Wide Association Study
Abstract: We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10(-7) to P = 4 × 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
Published: 2009
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26. Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest

Author: Pappas, D J, primary, Lizee, A, additional, Paunic, V, additional, Beutner, K R, additional, Motyer, A, additional, Vukcevic, D, additional, Leslie, S, additional, Biesiada, J, additional, Meller, J, additional, Taylor, K D, additional, Zheng, X, additional, Zhao, L P, additional, Gourraud, P-A, additional, Hollenbach, J A, additional, Mack, S J, additional, and Maiers, M, additional
Published: 2017
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27. Imputation of KIR Types from SNP Variation Data

Author: Vukcevic, D, Traherne, J, Næss, S, Ellinghaus, E, Kamatani, Y, Dilthey, A, Lathrop, M, Karlsen, T, Franke, A, Moffatt, M, Cookson, W, Trowsdale, J, McVean, G, Sawcer, S, Leslie, S, Traherne, James [0000-0002-6003-8559], Trowsdale, John [0000-0002-0150-5698], Sawcer, Stephen [0000-0001-7685-0974], Apollo - University of Cambridge Repository, and Wellcome Trust
Subjects: Male, NK CELL RECEPTORS, DNA Copy Number Variations, Genotype, LOCI, chemical and pharmacologic phenomena, SUSCEPTIBILITY, ERAP1, Polymorphism, Single Nucleotide, DISEASE, Dermatitis, Atopic, Cohort Studies, Receptors, KIR, Genetics, otorhinolaryngologic diseases, Humans, Genetics(clinical), Family, Genetic Predisposition to Disease, Genetics & Heredity, RISK, CLASSICAL HLA ALLELES, Science & Technology, High-Throughput Nucleotide Sequencing, hemic and immune systems, 11 Medical And Health Sciences, Sequence Analysis, DNA, 06 Biological Sciences, Asthma, Europe, Case-Control Studies, LIGANDS, Female, Life Sciences & Biomedicine
Abstract: Large population studies of immune system genes are essential for characterizing their role in diseases, including autoimmune conditions. Of key interest are a group of genes encoding the killer cell immunoglobulin-like receptors (KIRs), which have known and hypothesized roles in autoimmune diseases, resistance to viruses, reproductive conditions, and cancer. These genes are highly polymorphic, which makes typing expensive and time consuming. Consequently, despite their importance, KIRs have been little studied in large cohorts. Statistical imputation methods developed for other complex loci (e.g., human leukocyte antigen [HLA]) on the basis of SNP data provide an inexpensive high-throughput alternative to direct laboratory typing of these loci and have enabled important findings and insights for many diseases. We present KIR∗IMP, a method for imputation of KIR copy number. We show that KIR∗IMP is highly accurate and thus allows the study of KIRs in large cohorts and enables detailed investigation of the role of KIRs in human disease.
Published: 2015

28. Serum iron levels and the risk of Parkinson Disease: a Mendelian randomization study

Author: Pichler I, Del Greco M. F, Gögele M, Lill CM, Bertram L, Do CB, Eriksson N, Foroud T, Myers RH, PD GWAS Consortium, Nalls M, Keller MF, International Parkinson's Disease Genomics Consortium, Wellcome Trust Case Control Consortium 2, Benyamin B, Whitfield JB, Genetics of Iron Status Consortium, Pramstaller PP, Hicks AA, Thompson JR, Minelli C., Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón Sánchez J, Schulte C, Lesage S, Arepalli S, Barker R, Ben Shlomo Y, Berendse HW, Berg D, Bhatia K, de Bie RM, Biffi A, Bloem B, Bochdanovits Z, Bonin M, Bras JM, Brockmann K, Brooks J, Burn DJ, Charlesworth G, Chen H, Chinnery PF, Chong S, Clarke CE, Cookson MR, Cooper JM, Corvol JC, Counsell C, Damier P, Dartigues JF, Deloukas P, Deuschl G, Dexter DT, van Dijk KD, Dillman A, Durif F, Dürr A, Edkins S, Evans JR, Foltynie T, Gao J, Gardner M, Gibbs JR, Goate A, Gray E, Guerreiro R, Harris C, van Hilten JJ, Hofman A, Hollenbeck A, Holton J, Hu M, Huang X, Huber H, Hudson G, Hunt SE, Illig T, Lambert JC, Langford C, Lees A, Lichtner P, Limousin P, Lopez G, Lorenz D, McNeill A, Moorby C, Moore M, Morris HR, Morrison KE, Mudanohwo E, O'Sullivan SS, Pearson J, Perlmutter JS, Pollak P, Post B, Potter S, Ravina B, Revesz T, Riess O, Rivadeneira F, Rizzu P, Ryten M, Sawcer S, Schapira A, Scheffer H, Shaw K, Shoulson I, Sidransky E, Smith C, Spencer CC, Stockton JD, Strange A, Talbot K, Tanner CM, Tashakkori Ghanbaria A, Trabzuni D, Traynor BJ, Uitterlinden AG, Velseboer D, Vidailhet M, Walker R, van de Warrenburg B, Wickremaratchi M, Williams N, Williams Gray CH, Winder Rhodes S, Martinez M, Hardy J, Heutink P, Brice A, Gasser T, Singleton AB, Wood NW, Donnelly P, Barroso I, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Band G, Bellenguez C, Freeman C, Hellenthal G, Giannoulatou E, Pirinen M, Pearson R, Su Z, Vukcevic D, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Hammond N, Jayakumar A, McCann OT, Liddle J, Potter SC, Ravindrarajah R, Ricketts M, Waller M, Weston P, Widaa S, Whittaker P, McCarthy MI, Ouwehand WH, Radhakrishnan A, Sambrook J, Toniolo D, Camaschella C, Metspalu A, Esko T, Gieger C, Ried J, Meitinger T, Oexle K, Winkelmann J, Swinkels D, Vermeulen S, van Duijn C, Broer L, Beilby J, Hui J, Anderson D, Visscher P, Martin N., TRAGLIA, MICHELA, Pichler, Irene, Del Greco M, Fabiola, Gögele, Martin, Lill, Christina M, Benyamin, Beben, Minelli, Cosetta, PD GWAS Consortium, International Parkinson’s Disease Genomics Consortium, Wellcome Trust Case Control Consortium, Genetics of Iron Status Consortium, Pollak, Pierre, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Human genetics, NCA - Brain mechanisms in health and disease, ANS - Amsterdam Neuroscience, Neurology, Graduate School, Pichler, I, Del Greco M., F, Gögele, M, Lill, Cm, Bertram, L, Do, Cb, Eriksson, N, Foroud, T, Myers, Rh, PD GWAS, Consortium, Nalls, M, Keller, Mf, International Parkinson's Disease Genomics, Consortium, Wellcome Trust Case Control Consortium, 2, Benyamin, B, Whitfield, Jb, Genetics of Iron Status, Consortium, Pramstaller, Pp, Hicks, Aa, Thompson, Jr, Minelli, C., Plagnol, V, Hernandez, Dg, Sharma, M, Sheerin, Um, Saad, M, Simón Sánchez, J, Schulte, C, Lesage, S, Arepalli, S, Barker, R, Ben Shlomo, Y, Berendse, Hw, Berg, D, Bhatia, K, de Bie, Rm, Biffi, A, Bloem, B, Bochdanovits, Z, Bonin, M, Bras, Jm, Brockmann, K, Brooks, J, Burn, Dj, Charlesworth, G, Chen, H, Chinnery, Pf, Chong, S, Clarke, Ce, Cookson, Mr, Cooper, Jm, Corvol, Jc, Counsell, C, Damier, P, Dartigues, Jf, Deloukas, P, Deuschl, G, Dexter, Dt, van Dijk, Kd, Dillman, A, Durif, F, Dürr, A, Edkins, S, Evans, Jr, Foltynie, T, Gao, J, Gardner, M, Gibbs, Jr, Goate, A, Gray, E, Guerreiro, R, Harris, C, van Hilten, Jj, Hofman, A, Hollenbeck, A, Holton, J, Hu, M, Huang, X, Huber, H, Hudson, G, Hunt, Se, Illig, T, Lambert, Jc, Langford, C, Lees, A, Lichtner, P, Limousin, P, Lopez, G, Lorenz, D, Mcneill, A, Moorby, C, Moore, M, Morris, Hr, Morrison, Ke, Mudanohwo, E, O'Sullivan, S, Pearson, J, Perlmutter, J, Pollak, P, Post, B, Potter, S, Ravina, B, Revesz, T, Riess, O, Rivadeneira, F, Rizzu, P, Ryten, M, Sawcer, S, Schapira, A, Scheffer, H, Shaw, K, Shoulson, I, Sidransky, E, Smith, C, Spencer, Cc, Stockton, Jd, Strange, A, Talbot, K, Tanner, Cm, Tashakkori Ghanbaria, A, Trabzuni, D, Traynor, Bj, Uitterlinden, Ag, Velseboer, D, Vidailhet, M, Walker, R, van de Warrenburg, B, Wickremaratchi, M, Williams, N, Williams Gray, Ch, Winder Rhodes, S, Martinez, M, Hardy, J, Heutink, P, Brice, A, Gasser, T, Singleton, Ab, Wood, Nw, Donnelly, P, Barroso, I, Blackwell, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Duncanson, A, Jankowski, J, Markus, H, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Su, Z, Vukcevic, D, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Mccarthy, Mi, Ouwehand, Wh, Radhakrishnan, A, Sambrook, J, Toniolo, D, Traglia, Michela, Camaschella, C, Metspalu, A, Esko, T, Gieger, C, Ried, J, Meitinger, T, Oexle, K, Winkelmann, J, Swinkels, D, Vermeulen, S, van Duijn, C, Broer, L, Beilby, J, Hui, J, Anderson, D, Visscher, P, and Martin, N.
Subjects: Relative risk reduction, Iron, Mendelian randomization analysis, Physiology, Genome-wide association study, Biology, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, SDG 17 - Partnerships for the Goals, Risk Factors, Mendelian randomization, medicine, Humans, Genetic Predisposition to Disease, Iron/blood, Genetic Association Studies, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Parkinson Disease/blood/genetics, Confounding, Parkinson Disease, Mendelian Randomization Analysis, General Medicine, Iron metabolism, 3. Good health, ddc:616.8, Parkinson disease, Meta-analysis, Hereditary hemochromatosis, Serum iron, Medicine, 030217 neurology & neurosurgery, Research Article
Abstract: In this study, Mendelian randomization was used to study genes known to modify iron levels, and the effect of iron on Parkinson's disease (PD) risk was estimated. Based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date, the findings suggest that increased iron levels in the blood are associated with a 3% reduction in the risk of Parkinson's disease for every 10 µg/dL increase in iron. The results of this analysis have potentially important implications for future research into the prevention of Parkinson's disease. Please see later in the article for the Editors' Summary, Background Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date. Methods and Findings We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron. Conclusions Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made. Please see later in the article for the Editors' Summary, Editors' Summary Background Parkinson disease is a degenerative disorder of the central nervous system caused by the death of dopamine-generating cells in the substania nigra, a region of the midbrain. The earliest symptoms are usually movement-related and include tremor, slow movements, and difficulty walking, and later cognitive and behavioral problems may arise, with dementia commonly occurring in the advanced stages of the disease. Parkinson disease affects around ten million people world-wide and incidence increases with age, with men more affected than women. To date, the causes of Parkinson disease remain unknown although a combination of genetic and environmental factors is thought to play a role. Identifying possible modifiable risks is an important step in the possible prevention of Parkinson disease. Why Was This Study Done? Previous studies have shown a possible association between lower blood levels of iron in people with Parkinson disease compared with controls, although the quality of these studies makes this finding difficult to interpret. So in this study, the researchers used a mendelian randomization approach to investigate whether there was any evidence of an effect of blood iron levels on the risk of Parkinson disease and if so to further explore the direction and scale of any link. Mendelian randomization is a method of using measured variation in genes of known function to examine the causal effect of a modifiable exposure on disease in situations where it is inappropriate to perform a randomized controlled trial. What Did the Researchers Do and Find? The researchers estimated the effect of blood iron levels on the risk of Parkinson disease using three polymorphisms in two genes, HFE and TMPRSS6. For each polymorphism, they performed a meta-analysis combining the results of studies investigating the genetic effect on iron levels, which included almost 22,000 people from Europe and Australia, and a meta-analysis of studies investigating the genetic effect on the risk of Parkinson disease, which included a total of 20,809 people with Parkinson disease and 88,892 controls from Europe and North America. They then performed three separate mendelian randomization analyses to estimate the effect of iron on Parkinson disease for the three polymorphisms. By combining the three estimates, they obtained a statistically significant odds ratio of 0.97 for Parkinson disease per 10 µg/dl increase in iron, corresponding to a 3% reduction in the risk of Parkinson disease for every 10 µg/dl increase in blood iron. Since genotype influences on blood iron levels represent differences that generally persist throughout adult life, the combined mendelian randomization estimate reflects an effect of iron over the course of a lifetime. What Do These Findings Mean? These findings suggest that increased iron levels in the blood are associated with a 3% reduction in the risk of Parkinson disease for every 10 µg/dl increase in iron. This finding is important as it suggests that increased blood iron levels may have a protective effect against Parkinson disease, although the underlying mechanism remains unclear. Furthermore, although mendelian randomization is an increasingly used approach to address the issue of classical confounding, there may be remaining confounding factors specific of mendelian randomization that may influence the interpretation of this study. Nevertheless, the results of this analysis have potentially important implications for future research into the prevention of Parkinson disease. Further studies on the underlying mechanisms are needed before any specific treatment recommendations can be proposed. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001462. The National Institutes of Neurological Disorder and Stroke, MedlinePlus, and NHS Choices have several pages with comprehensive information on Parkinson disease Wikipedia gives an explanation of mendelian randomization (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Published: 2013
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29. Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank

Author: Cortes, A, Dendrou, CA, Motyer, A, Jostins, L, Vukcevic, D, Dilthey, A, Donnelly, P, Leslie, S, Fugger, L, McVean, G, Cortes, A, Dendrou, CA, Motyer, A, Jostins, L, Vukcevic, D, Dilthey, A, Donnelly, P, Leslie, S, Fugger, L, and McVean, G
Abstract: Genetic discovery from the multitude of phenotypes extractable from routine healthcare data can transform understanding of the human phenome and accelerate progress toward precision medicine. However, a critical question when analyzing high-dimensional and heterogeneous data is how best to interrogate increasingly specific subphenotypes while retaining statistical power to detect genetic associations. Here we develop and employ a new Bayesian analysis framework that exploits the hierarchical structure of diagnosis classifications to analyze genetic variants against UK Biobank disease phenotypes derived from self-reporting and hospital episode statistics. Our method displays a more than 20% increase in power to detect genetic effects over other approaches and identifies new associations between classical human leukocyte antigen (HLA) alleles and common immune-mediated diseases (IMDs). By applying the approach to genetic risk scores (GRSs), we show the extent of genetic sharing among IMDs and expose differences in disease perception or diagnosis with potential clinical implications.
Published: 2017

30. Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1

Author: Martino, DJ, Ashley, S, Koplin, J, Ellis, J, Saffery, R, Dharmage, SC, Gurrin, L, Matheson, MC, Kalb, B, Marenholz, I, Beyer, K, Lee, Y-A, Hong, X, Wang, X, Vukcevic, D, Motyer, A, Leslie, S, Allen, KJ, Ferreira, MAR, Martino, DJ, Ashley, S, Koplin, J, Ellis, J, Saffery, R, Dharmage, SC, Gurrin, L, Matheson, MC, Kalb, B, Marenholz, I, Beyer, K, Lee, Y-A, Hong, X, Wang, X, Vukcevic, D, Motyer, A, Leslie, S, Allen, KJ, and Ferreira, MAR
Abstract: BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P ≤ 5 × 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.
Published: 2017

31. Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction

Author: Lucas G1, Lluís-Ganella C, Subirana I, Musameh MD, Gonzalez JR, Nelson CP, Sentí M, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Schwartz SM, Siscovick D, O'Donnell CJ, Melander O, Salomaa V, Purcell S, Altshuler D, Samani NJ, Kathiresan S, Elosua R, Voight BF, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, Peltonen L, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Yee J, Friedlander Y, Marrugat J, Lucas G, Sala J, Ramos R, Meigs JB, Williams G, Nathan DM, MacRae CA, Havulinna AS, Berglund G, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Stratton MR, Todd JA, Worthington J, Burton PR, Clayton DG, Cardon LR, Craddock N, Duncanson A, Barrett JC, Davison D, Easton D, Evans D, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Ball SG, Balmforth AJ, Barrett JH, Bishop D, Iles MM, Maqbool A, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Cardo LR, Cardin NJ, Ferreira T, Pereira-Gale J, Hallgrimsdottir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Lucas, G1, Lluís-Ganella, C, Subirana, I, Musameh, Md, Gonzalez, Jr, Nelson, Cp, Sentí, M, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Schwartz, Sm, Siscovick, D, O'Donnell, Cj, Melander, O, Salomaa, V, Purcell, S, Altshuler, D, Samani, Nj, Kathiresan, S, Elosua, R, Voight, Bf, Musunuru, K, Ardissino, D, Mannucci, Pm, Anand, S, Engert, Jc, Schunkert, H, Erdmann, J, Reilly, Mp, Rader, Dj, Morgan, T, Spertus, Ja, Stoll, M, Girelli, D, Mckeown, Pp, Patterson, Cc, Peltonen, L, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Lucas, G, Sala, J, Ramos, R, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, Havulinna, A, Berglund, G, Deloukas, P, Donnelly, P, Farrall, M, Gough, Sc, Hall, A, Hattersley, At, Hill, Av, Kwiatkowski, Dp, Mathew, Cg, Mccarthy, Mi, Ouwehand, Wh, Parkes, M, Pembrey, M, Rahman, N, Stratton, Mr, Todd, Ja, Worthington, J, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Duncanson, A, Barrett, Jc, Davison, D, Easton, D, Evans, D, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Ball, Sg, Balmforth, Aj, Barrett, Jh, Bishop, D, Iles, Mm, Maqbool, A, Braund, P, Dixon, Rj, Mangino, M, Stevens, S, Thompson, Jr, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Cardo, Lr, Cardin, Nj, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, Ib, Howie, Bn, Su, Z, Teo, Yy, and Vukcevic, D
Subjects: Heredity, Epidemiology, Myocardial Infarction, lcsh:Medicine, Genome-wide association study, Coronary Artery Disease, Cardiovascular, Logistic regression, Risk Factors, Cardiac and Cardiovascular Systems, lcsh:Science, Genetics, 0303 health sciences, Multidisciplinary, Medicine (all), 030305 genetics & heredity, Genomics, Genetic Epidemiology, Medicine, Research Article, Human, Risk, Genotype, Genotypes, Reproducibility of Result, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genome Analysis Tools, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Risk factor, Allele frequency, Genetic Association Studies, 030304 developmental biology, Genetic association, Biochemistry, Genetics and Molecular Biology (all), Complex Traits, Risk Factor, lcsh:R, Reproducibility of Results, Human Genetics, Epistasis, Genetic, Odds ratio, Genetic epidemiology, Agricultural and Biological Sciences (all), Genetics of Disease, Epistasis, Genetic Polymorphism, Infart de miocardi -- Epidemiologia, lcsh:Q, Population Genetics, Genome-Wide Association Study
Abstract: The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3–2.0, depending on allele frequency and interaction model).
Published: 2012
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32. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies

Author: Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Braund PS, Wright B, Balmforth AJ, Ball SG, Chen L, Wells GA, McPherson R, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Absher D, Hlatky MA, Iribaren C, Knowles JW, Linsel Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Su S, Bouzyk M, Vaccarino V, Zafari AM, Carlquist JF, Muhlestein JB, Olivieri O, Barnard J, Hartiala J, Tang WH, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Dixon RJ, Mangino M, Stevens S, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop M, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira Gale J, Hallgrimsdóttir IB, Bowie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, CASARI , GIORGIO NEVIO, Reilly, Mp, Li, M, He, J, Ferguson, Jf, Stylianou, Im, Mehta, Nn, Burnett, M, Devaney, Jm, Knouff, Cw, Thompson, Jr, Horne, Bd, Stewart, Af, Assimes, Tl, Wild, P, Allayee, H, Nitschke, Pl, Patel, R, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Martinelli, N, Girelli, D, Quyyumi, Aa, Anderson, Jl, Erdmann, J, Hall, A, Schunkert, H, Quertermous, T, Blankenberg, S, Hazen, Sl, Roberts, R, Kathiresan, S, Samani, Nj, Epstein, Se, Rader, Dj, Qasim, An, Derohannessian, Sl, Qu, L, Cappola, Tp, Chen, Z, Matthai, W, Hakonarson, Hh, Wilensky, R, Kent, Km, Lindsay, Jm, Pichard, Ad, Satler, L, Waksman, R, Knoupf, Cw, Walker, Mc, Waterworth, Dm, Mosser, V, Braund, P, Wright, B, Balmforth, Aj, Ball, Sg, Chen, L, Wells, Ga, Mcpherson, R, Lackner, K, Munzel, Tf, Schillert, A, Schnabel, R, Zeller, T, Ziegler, A, Absher, D, Hlatky, Ma, Iribaren, C, Knowles, Jw, Linsel Nitschke, P, König, Ir, Hengstenberg, C, Nahrstaedt, J, Peters, A, Schreiber, S, Wichmann, E, Willenborg, C, Su, S, Bouzyk, M, Vaccarino, V, Zafari, Am, Carlquist, Jf, Muhlestein, Jb, Olivieri, O, Barnard, J, Hartiala, J, Tang, Wh, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, Dp, Mccarthy, Mi, Ouwehand, Wh, Todd, Ja, Donnelly, P, Barrett, Jc, Davison, D, Easton, D, Evans, Dm, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon Smith, K, Jones, L, Fraser, C, Green, Ek, Grozeva, D, Hamshere, Ml, Holmans, Pa, Jones, Ir, Kirov, G, Moskvina, V, Nikolov, I, O'Donovan, Mc, Owen, Mj, Collier, Da, Elkin, A, Farmer, A, Williamson, R, Mcguffin, P, Young, Ah, Ferrier, In, Barrett, Jh, Bishop, Dt, Iles, Mm, Maqbool, A, Yuldasheva, N, Dixon, Rj, Mangino, M, Stevens, S, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, Cw, Nimmo, Er, Satsangi, J, Fisher, Sa, Forbes, A, Lewis, Cm, Onnie, Cm, Prescott, Nj, Sanderson, J, Mathew, Cg, Barbour, J, Mohiuddin, Mk, Todhunter, Ce, Mansfield, Jc, Ahmad, T, Cummings, Fr, Jewell, Dp, Webster, J, Brown, Mj, Lathrop, M, Connell, J, Dominiczak, A, Marcano, Ca, Burke, B, Dobson, R, Gungadoo, J, Lee, Kl, Munroe, Pb, Newhouse, Sj, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, In, Donovan, H, Eyre, S, Gilbert, Pd, Hider, Sl, Hinks, Am, John, Sl, Potter, C, Silman, Aj, Symmons, Dp, Thomson, W, Worthington, J, Dunger, Db, Widmer, B, Frayling, Tm, Freathy, Rm, Lango, H, Perry, Jr, Shields, Bm, Weedon, Mn, Hattersley, At, Hitman, Ga, Walker, M, Elliott, K, Groves, Cj, Lindgren, Cm, Rayner, Nw, Timpson, Nj, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, Av, Bradbury, La, Farrar, C, Pointon, Jj, Wordsworth, P, Brown, Ma, Franklyn, Ja, Heward, Jm, Simmonds, Mj, Gough, Sc, Seal, S, Stratton, Mr, Rahman, N, Ban, M, Goris, A, Sawcer, Sj, Compston, A, Conway, D, Jallow, M, Rockett, Ka, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, Nj, Ferreira, T, Pereira Gale, J, Hallgrimsdóttir, Ib, Bowie, Bn, Su, Z, Teo, Yy, Vukcevic, D, Bentley, D, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, GIORGIO NEVIO, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, D, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, A, Peltonen, L, Melander, O, Berglund, G, Voight, Bf, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Daly, Mj, Purcell, S, Surti, A, Guiducci, C, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, and Gabriel, Sb
Subjects: Adult, Male, medicine.medical_specialty, Linkage disequilibrium, ABO, ADAMTS7 Protein, ADAMTS7, Genome-wide association study, Coronary Angiography, Polymorphism, Single Nucleotide, Linkage Disequilibrium, ABO Blood-Group System, Coronary artery disease, Gene Frequency, ABO blood group system, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Myocardial infarction, Genetic risk factor, genetic locus, Coronary atherosclerosis, Aged, business.industry, coronary atherosclerosis, General Medicine, Middle Aged, medicine.disease, ADAM Proteins, myocardial infarction, Genetic Loci, Cardiology, Myocardial infarction complications, Female, business, coronary artery disease, Genome-Wide Association Study
Abstract: BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
Published: 2011

33. The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Author: Davis, O, Band, G, Pirinen, M, Haworth, C, Meaburn, E, Kovas, Y, Harlaar, N, Docherty, S, Hanscombe, K, Trzaskowski, M, Curtis, C, Strange, A, Freeman, C, Bellenguez, C, Su, Z, Pearson, R, Vukcevic, D, Langford, C, Deloukas, P, Hunt, S, Gray, E, Dronov, S, Potter, S, Tashakkori-Ghanbaria, A, Edkins, S, Bumpstead, S, Blackwell, J, Bramon, E, Brown, M, Casas, J, Corvin, A, Duncanson, A, Jankowski, J, Markus, H, Mathew, C, Palmer, C, Rautanen, A, Sawcer, S, Trembath, R, Viswanathan, A, Wood, N, Barroso, I, Peltonen, L, Dale, P, Petrill, SA, Schalkwyk, L, Craig, I, Lewis, C, Price, T, Donnelly, P, Plomin, R, Spencer, C, and Consortium, The Wellcome Trust Case Control
Abstract: Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve., Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve.
Published: 2014

34. Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms inHLA ‐ DRB 1

Author: Martino, D. J., primary, Ashley, S., additional, Koplin, J., additional, Ellis, J., additional, Saffery, R., additional, Dharmage, S. C., additional, Gurrin, L., additional, Matheson, M. C., additional, Kalb, B., additional, Marenholz, I., additional, Beyer, K., additional, Lee, Y.‐A., additional, Hong, X., additional, Wang, X., additional, Vukcevic, D., additional, Motyer, A., additional, Leslie, S., additional, Allen, K. J., additional, and Ferreira, M. A. R., additional
Published: 2017
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35. Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease

Author: Robinson, PC, Leo, PJ, Pointon, JJ, Harris, J, Cremin, K, Bradbury, LA, Stebbings, S, Harrison, AA, Duncan, EL, Evans, DM, Wordsworth, PB, Brown, MA, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CN, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CC, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Spencer, CCA, McCloskey, E, Eisman, J, Jones, G, Nicholson, G, Eastell, R, Sambrook, P, Prince, R, Dennison, E, Reid, I, Wark, J, Robinson, PC, Leo, PJ, Pointon, JJ, Harris, J, Cremin, K, Bradbury, LA, Stebbings, S, Harrison, AA, Duncan, EL, Evans, DM, Wordsworth, PB, Brown, MA, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CN, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CC, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Spencer, CCA, McCloskey, E, Eisman, J, Jones, G, Nicholson, G, Eastell, R, Sambrook, P, Prince, R, Dennison, E, Reid, I, and Wark, J
Abstract: Ankylosing spondylitis (AS) is a common chronic immune-mediated arthropathy affecting primarily the spine and pelvis. The condition is strongly associated with HLA-B*27 as well as other human leukocyte antigen variants and at least 47 individual non-MHC-associated variants. However, substantial additional heritability remains as yet unexplained. To identify further genetic variants associated with the disease, we undertook an association study of AS in 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. A novel association achieving genome-wide significance was noted at CDKAL1. Suggestive associations were demonstrated with common variants in FAM118A, C7orf72 and FAM114A1 and with a low-frequency variant in PNPLA1. Two of the variants have been previously associated with inflammatory bowel disease (IBD; CDKAL1 and C7orf72). These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having similar aetiopathogenesis.
Published: 2016

36. Temporal clustering of rotational glitches in the Crab pulsar.

Author: Carlin, J B, Melatos, A, and Vukcevic, D
Subjects: PULSARS, STELLAR populations, GALAXY clusters, STELLAR magnetic fields, STELLAR chromospheres
Abstract: It is an open question whether glitch activity in individual pulsars varies on decadal time-scales. The Crab pulsar has experienced 23 spin-up glitches in the last 36 yr, interrupting an otherwise monotonic deceleration. A homogeneous Poisson process, i.e. a process with constant rate, is not sufficient to describe the time-ordered distribution of glitch epochs in the Crab pulsar. There are signs of clustering at the 2σ level when testing with Ripley's K function. Two alternative, inhomogeneous models with one and two step-wise rate changes are found to have higher relative evidence (Bayes factors of 1.74 and 2.86, respectively) than the homogeneous Poisson process. The distinction between clustering, where events are correlated, and rate variation is discussed. The implications for glitch microphysics, in particular trigger mechanisms based on avalanche processes, are briefly discussed. [ABSTRACT FROM AUTHOR]
Published: 2019
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37. Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

Author: (BMES), Blue Mountains Eye Study, (WTCCC2), Wellcome Trust Case Control Consortium 2, Strange, A, Bellenguez, C, Freeman, C, Pirinen, M, Su, Z, Band, G, Pearson, R, Vukcevic, D, Rautanen, A, Spencer, C, and Donnelly, P
Subjects: genetic structures, sense organs, eye diseases
Abstract: To discover quantitative trait loci for intraocular pressure, a major risk factor for glaucoma and the only modifiable one, we performed a genome-wide association study on a discovery cohort of 2175 individuals from Sydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, P(combined) = 1.10 × 10(-8)). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.
Published: 2013

38. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Author: Ripke, S, O'Dushlaine, C, Chambert, K, Moran, Jl, Kähler, Ak, Akterin, S, Bergen, Se, Collins, Al, Crowley, Jj, Fromer, M, Kim, Y, Lee, Sh, Magnusson, Pk, Sanchez, N, Stahl, Ea, Williams, S, Wray, Nr, Xia, K, Bettella, F, Borglum, Ad, Bulik Sullivan, Bk, Cormican, P, Craddock, N, Leeuw, De, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, Ml, Holmans, P, Hougaard, Dm, Kendler, Ks, Lin, K, Morris, Dw, Mors, O, Mortensen, Pb, Neale, Bm, O'Neill, Fa, Owen, Mj, Milovancevic, Mp, Posthuma, D, Powell, J, Richards, Al, Riley, Bp, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, Ab, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, Sarah, Verhage, M, Walters, Jt, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, Df, Gejman, Pv, Laurent, C, Mowry, Bj, O'Donovan, Mc, Pulver, Ae, Schwab, Sg, Wildenauer, Db, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, Fb, Liang, Ky, Maier, W, Mallet, J, Nertney, Da, Nestadt, G, Norton, N, Papadimitriou, Gn, Ribble, R, Sanders, Ar, Silverman, Jm, Walsh, D, Williams, Nm, Wormley, B, Psychosis Endophenotypes International Consortium, Arranz, Mj, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, Rs, Kalaydjieva, L, Lawrie, S, Lewis, Cm, Linszen, Dh, Mata, I, Mcintosh, A, Murray, Rm, Ophoff, Ra, Van, Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Wellcome Trust Case Control Consortium 2, Donnelly, P, Barroso, I, Blackwell, Jm, Brown, Ma, Casas, Jp, Corvin, Ap, Deloukas, P, Duncanson, A, Jankowski, J, Markus, Hs, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, Rd, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Tashakkori Ghanbaria, A, Waller, Mj, Weston, P, Widaa, S, Whittaker, P, Mccarthy, Mi, Stefansson, K, Scolnick, E, Purcell, S, Mccarroll, Sa, Sklar, P, Hultman, Cm, Sullivan, P. F., Functional Genomics, Molecular and Cellular Neurobiology, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Adult Psychiatry, Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Lee, Sang Hong, Sullivan, Patrick F, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA deCODE Genet, Reykjavik, Iceland Aarhus Univ Hosp, Risskov, Denmark Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia Statens Serum Inst, DK-2300 Copenhagen, Denmark Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Kings Coll London, Inst Psychiat, London, England Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, DenmarkQueens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Belgrade, Fac Med, Belgrade, Serbia Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands Kings Coll London, Dept Neurosci, London, England Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA Univ Halle, Dept Psychiat, Halle, Germany Univ Munich, Dept Psychiat, D-80539 Munich, Germany Univ Iceland, Dept Psychiat, Reykjavik, Iceland Landspitali University Hospital Reykjavik, Iceland Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Rep of Georgia Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Verona, Sect Psychiat, I-37100 Verona, Italy UCL, Inst Cognit Neurosci, London, England UCL, Mental Hlth Sci Unit, London, England Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Genet, Boston, MA USA, Child and Adolescent Psychiatry / Psychology, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Human genetics, NCA - Brain mechanisms in health and disease, and NCA - Neurobiology of mental health
Subjects: Male, Candidate gene, SNP, Single-nucleotide polymorphism, Genome-wide association study, Disease, Biology, heritability, neuronal calcium signaling, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Genetics, medicine, Humans, GWAS, Genetic Predisposition to Disease, Bipolar disorder, 030304 developmental biology, Genetic association, Sweden, Genetics & Heredity, 0303 health sciences, medicine.disease, 3. Good health, genome sequencing, schizophrenia, Schizophrenia, Meta-analysis, Case-Control Studies, genetic variation, Female, genome-wide scan, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder. NIMH R01 MH077139 R01 MH095034 Stanley Center for Psychiatric Research Sylvan Herman Foundation Friedman Brain Institute at the Mount Sinai School of Medicine Karolinska Institutet, Karolinska University Hospital Swedish Research Council Swedish County Council Soderstrom Konigska Foundation Netherlands Scientific Organization NWO 645-000-003 info:eu-repo/grantAgreement/EC/FP7/223423 Danish Strategic Research Council H. Lundbeck A/S Faculty of Health Sciences at Aarhus University Lundbeck Foundation Stanley Research Foundation Wellcome Trust 085475/B/08/Z 085475/Z/08/Z
Published: 2013
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39. Bayesian refinement of association signals for 14 loci in 3 common diseases

Author: Maller, JB, McVean, G, Byrnes, J, Vukcevic, D, Palin, K, Su, Z, Howson, JMM, Auton, A, Myers, S, Morris, A, Pirinen, M, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Craddock, N, Hurles, M, Ouwehand, W, Parkes, M, Rahman, N, Duncanson, A, Todd, JA, Kwiatkowski, DP, Samani, NJ, Gough, SCL, McCarthy, MI, Deloukas, P, and Donnelly, P
Subjects: endocrine system diseases, Posterior probability, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Single-nucleotide polymorphism, Genome-wide association study, Coronary Artery Disease, Biology, FTO gene, Polymorphism, Single Nucleotide, Article, Bayes' theorem, Genetics, Humans, CTLA-4 Antigen, Genetic Predisposition to Disease, Genetic association, Cyclin-Dependent Kinase Inhibitor p15, Homeodomain Proteins, tRNA Methyltransferases, Genes, p16, Proteins, nutritional and metabolic diseases, Bayes Theorem, Cyclin-Dependent Kinase 5, Graves Disease, TRNA Methyltransferases, Diabetes Mellitus, Type 2, Genetic Loci, TCF7L2, Transcription Factor 7-Like 2 Protein, Genome-Wide Association Study, Transcription Factors
Abstract: To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.
Published: 2012
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40. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Author: Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., Mcgovern, Dermot P., Hui, Ken Y., Lee, James C., Philip Schumm, L., Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Xinli, Hu, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C., Cho, Judy H., Barclay, M, Peyrin Biroulet, L, Chamaillard, M, Colombel, Jf, Cottone, M, Croft, A, D'Incà, R, Halfvarson J, Hanigan K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lémann, M, Levine, A, Massey, D, Milla, M, Montgomery, Gw, Ng, Sm, Oikonomou, I, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, Laura, Taylor, Km, Törkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Andrews, Jm, Bampton, Pa, Florin, Th, Gearry, R, Krishnaprasad, K, Lawrance, Ic, Mahy, G, Radford Smith, G, Roberts, Rl, Simms, La, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie AM 3rd, Beck, K, Bernard, Ej, Binion, Dg, Bitton, A, Brant, Sr, Cho, Jh, Cohen, A, Croitoru, K, Daly, Mj, Datta, Lw, Deslandres, C, Duerr, Rh, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, Gr, Haritunians, T, Jobin, G, Katz, S, Lahaie, Rg, Mcgovern, Dp, Nelson, L, Ning, K, Paré, P, Regueiro, Md, Rioux, Jd, Ruggiero, E, Schumm, L, Schwartz, M, Scott, R, Sharma, Y, Silverberg, Ms, Spears, D, Steinhart, A, Stempak, Jm, Swoger, Jm, Tsagarelis, C, Zhang, C, Zhao, H, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, Sg, Balmforth, Aj, Barnes, C, Barrett, Jc, Barroso, I, Barton, A, Bennett, Aj, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, Oj, Braund, Ps, Bredin, F, Breen, G, Brown, Mj, Bruce, In, Bull, J, Burren, Os, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, Cm, Coffey, Aj, Connell, Jm, Conrad, Df, Cooper, Jd, Dominiczak, Af, Downes, K, Drummond, He, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, Dm, Evans, G, Eyre, S, Farmer, A, Ferrier, In, Flynn, E, Forbes, A, Forty, L, Franklyn, Ja, Frayling, Tm, Freathy, Rm, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon Smith, K, Gray, E, Green, E, Groves, Cj, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, Ga, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, Jm, Hughes, D, Hunt, S, Isaacs, Jd, Jain, M, Jewell, Dp, Johnson, T, Jolley, Jd, Jones, Ir, Jones, La, Kirov, G, Langford, Cf, Lango Allen, H, Lathrop, Gm, Lee, J, Lee, Kl, Lees, C, Lewis, K, Lindgren, Cm, Maisuria Armer, M, Maller, J, Mansfield, J, Marchini, Jl, Martin, P, Massey, Dc, Mcardle, Wl, Mcguffin, P, Mclay, Ke, Mcvean, G, Mentzer, A, Mimmack, Ml, Morgan, Ae, Morris, Ap, Mowat, C, Munroe, Pb, Myers, S, Newman, W, Nimmo, Er, O'Donovan, Mc, Onipinla, A, Ovington, Nr, Owen, Mj, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, Jr, Phillips, A, Plagnol, V, Prescott, Nj, Prokopenko, I, Quail, Ma, Rafelt, S, Rayner, Nw, Reid, Dm, Renwick, A, Ring, Sm, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, Jg, Sanderson, Jd, Sawcer, Sj, Schuilenburg, H, Scott, Ce, Seal, S, Shaw Hawkins, S, Shields, Bm, Simmonds, Mj, Smyth, Dj, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, He, Stirrups, K, Stone, Ma, Strachan, Dp, Su, Z, Symmons, Dp, Thompson, Jr, Thomson, W, Tobin, Md, Travers, Me, Turnbull, C, Vukcevic, D, Wain, Lv, Walker, M, Walker, Nm, Wallace, C, Warren Perry, M, Watkins, Na, Webster, J, Weedon, Mn, Wilson, Ag, Woodburn, M, Wordsworth, Bp, Yau, C, Young, Ah, Zeggini, E, Brown, Ma, Burton, Pr, Caulfield, Mj, Compston, A, Farrall, M, Gough, Sc, Hall, As, Hattersley, At, Hill, Av, Mathew, Cg, Pembrey, M, Satsangi, J, Stratton, Mr, Worthington, J, Hurles, Me, Duncanson, A, Ouwehand, Wh, Parkes, M, Rahman, N, Todd, Ja, Samani, Nj, Kwiatkowski, Dp, Mccarthy, Mi, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, Jm, Bramon, E, Casas, Jp, Corvin, A, Jankowski, J, Markus, Hs, Palmer, Cn, Plomin, R, Rautanen, A, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Genome-wide association study, Disease, SUSCEPTIBILITY, Inflammatory bowel disease, NUMBER, 0302 clinical medicine, Crohn Disease, NETWORK, Genetics, 0303 health sciences, Multidisciplinary, Genomics, Ulcerative colitis, 3. Good health, Colitis, Ulcerative, Genetic Predisposition to Disease, Genome, Human, Haplotypes, Humans, Inflammatory Bowel Diseases, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Genome-Wide Association Study, Host-Pathogen Interactions, IRGM, Medical genetics, 030211 gastroenterology & hepatology, EXPRESSION, medicine.medical_specialty, Immunology, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], TUBERCULOSIS, 03 medical and health sciences, Medical research, medicine, Allele, METAANALYSIS, 030304 developmental biology, HYPER-IGE SYNDROME, MUTATIONS, medicine.disease, RISK LOCI, Genetic architecture, digestive system diseases
Abstract: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
Published: 2012
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41. A two-stage meta-analysis identifies several new loci for Parkinson's disease

Author: Plagnol, V., Nalls, M.A., Bras, J.M., Hernandez, D., Sharma, M., Sheerin, U.M., Saad, M., Simon-Sanchez, J., Schulte, C., Lesage, S., Sveinbjornsdottir, S., Amouyel, P., Arepalli, S., Band, G., Barker, R.A., Bellinguez, C., Ben-Shlomo, Y., Berendse, H.W., Berg, D., Bhatia, K.P., Bie, R.M. de, Biffi, A., Bloem, B.R., Bochdanovits, Z., Bonin, M., Brockmann, K., Brooks, J., Burn, D.J., Charlesworth, G., Chen, H., Chinnery, P.F., Chong, S., Clarke, C.E., Cookson, M.R., Cooper, J.M., Corvol, J.C., Counsell, J., Damier, P., Dartigues, J.F., Deloukas, P., Deuschl, G., Dexter, D.T., Dijk, K.D. van, Dillman, A., Durif, F., Durr, A., Edkins, S., Evans, J.R., Foltynie, T., Freeman, C., Gao, J., Gardner, M., Gibbs, J.R., Goate, A., Gray, E., Guerreiro, R., Gustafsson, O., Harris, C., Hellenthal, G., Hilten, J.J. van, Hofman, A., Hollenbeck, A., Holton, J.L., Hu, M., Huang, X., Huber, H, Hudson, G., Hunt, S.E., Huttenlocher, J., Illig, T., Jonsson, P.V., Langford, C., Lees, A.J., Lichtner, P., Limousin, P., Lopez, G., McNeill, A., Moorby, C., Moore, M., Morris, H.A., Morrison, K.E., Mudanohwo, E., O'Sullivan, S.S, Pearson, J., Pearson, R., Perlmutter, J., Petursson, H., Pirinen, M., Polnak, P., Post, B., Potter, S.C., Ravina, B., Revesz, T., Riess, O., Rivadeneira, F., Rizzu, P., Ryten, M., Sawcer, S.J., Schapira, A., Scheffer, H., Shaw, K., Shoulson, I., Sidransky, E., Silva, R. de, Smith, C., Spencer, C.C., Stefansson, H., Steinberg, S., Stockton, J.D., Strange, A., Su, Z., Talbot, K., Tanner, C.M., Tashakkori-Ghanbaria, A., Tison, F., Trabzuni, D., Traynor, B.J., Uitterlinden, A.G., Vandrovcova, J., Velseboer, D., Vidailhet, M., Vukcevic, D., Walker, R., Warrenburg, B.P.C. van de, Weale, M.E., Wickremaratchi, M., Williams, N., Williams-Gray, C.H., Winder-Rhodes, S., Stefansson, K., Martinez, M., Donnelly, P., Singleton, A.B., Hardy, J., Heutink, P., Brice, A., Gasser, T., and Wood, N.W.
Subjects: Functional Neurogenomics Human Movement & Fatigue [DCN 2], Genomic disorders and inherited multi-system disorders Functional Neurogenomics [IGMD 3], Functional Neurogenomics [DCN 2]
Abstract: Contains fulltext : 97597.pdf (Publisher’s version ) (Open Access) A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p
Published: 2011

42. The influence of sighing respirations on infant lung function measured using multiple breath washout gas mixing techniques

Author: Vukcevic, D, Carlin, JB, King, L, Hall, GL, Ponsonby, A-L, Sly, PD, Vuillermin, P, Ranganathan, S, Vukcevic, D, Carlin, JB, King, L, Hall, GL, Ponsonby, A-L, Sly, PD, Vuillermin, P, and Ranganathan, S
Abstract: There is substantial interest in studying lung function in infants, to better understand the early life origins of chronic lung diseases such as asthma. Multiple breath washout (MBW) is a technique for measuring lung function that has been adapted for use in infants. Respiratory sighs occur frequently in young infants during natural sleep, and in accordance with current MBW guidelines, result in exclusion of data from a substantial proportion of testing cycles. We assessed how sighs during MBW influenced the measurements obtained using data from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part of the wash-in phase (before the last 5 breaths) were not associated with differences in standard MBW measurements compared with tests without sighs. In contrast, sighs that occurred during the washout were associated with a small but discernible increase in magnitude and variability. For example, the mean lung clearance index increased by 0.36 (95% CI: 0.11-0.62) and variance increased by a multiplicative factor of 2 (95% CI: 1.6-2.5). The results suggest it is reasonable to include MBW data from testing cycles where a sigh occurs during the wash-in phase, but not during washout, of MBW. By recovering data that would otherwise have been excluded, we estimate a boost of about 10% to the final number of acceptable tests and 6% to the number of individuals successfully tested.
Published: 2015

43. The influence of sighing respirations on infant lung function measured using multiple breath washout gas mixing techniques

Author: Vukcevic, D., Carlin, J., King, L., Hall, Graham, Ponsonby, A., Sly, P., Vuillermin, P., Ranganathan, S., Vukcevic, D., Carlin, J., King, L., Hall, Graham, Ponsonby, A., Sly, P., Vuillermin, P., and Ranganathan, S.
Abstract: There is substantial interest in studying lung function in infants, to better understand the early life origins of chronic lung diseases such as asthma. Multiple breath washout (MBW) is a technique for measuring lung function that has been adapted for use in infants. Respiratory sighs occur frequently in young infants during natural sleep, and in accordance with current MBW guidelines, result in exclusion of data from a substantial proportion of testing cycles. We assessed how sighs during MBW influenced the measurements obtained using data from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part of the wash‐in phase (before the last 5 breaths) were not associated with differences in standard MBW measurements compared with tests without sighs. In contrast, sighs that occurred during the washout were associated with a small but discernible increase in magnitude and variability. For example, the mean lung clearance index increased by 0.36 (95% CI: 0.11–0.62) and variance increased by a multiplicative factor of 2 (95% CI: 1.6–2.5). The results suggest it is reasonable to include MBW data from testing cycles where a sigh occurs during the wash‐in phase, but not during washout, of MBW. By recovering data that would otherwise have been excluded, we estimate a boost of about 10% to the final number of acceptable tests and 6% to the number of individuals successfully tested.
Published: 2015

44. Genetic Loci for Retinal Arteriolar Microcirculation

Author: Xueling, Sim, Jensen, Richard A., Kamran Ikram, M., Mary Frances Cotch, Xiaohui, Li, Stuart, Macgregor, Jing, Xie, Albert Vernon Smith, Eric, Boerwinkle, Paul, Mitchell, Ronald, Klein, Klein, Barbara E. K., Glazer, Nicole L., Thomas, Lumley, Barbara, Mcknight, Psaty, Bruce M., de Jong, Paulus T. V. M., Albert, Hofman, Fernando, Rivadeneira, Uitterlinden, Andre G., van Duijn, Cornelia M., Thor, Aspelund, Gudny, Eiriksdottir, Harris, Tamara B., Fridbert, Jonasson, Launer, Lenore J., John, Attia, Baird, Paul N., Stephen, Harrap, Holliday, Elizabeth G., Michael, Inouye, Elena, Rochtchina, Scott, Rodney J., Ananth, Viswanathan, Guo, Li, Smith, Nicholas L., Wiggins, Kerri L., Kuo, Jane Z., Taylor, Kent D., Hewitt, Alex W., Martin, Nicholas G., Montgomery, Grant W., Cong, Sun, Young, Terri L., Mackey, David A., van Zuydam, Natalie R., Doney, Alex S. F., Palmer, Colin N. A., Morris, Andrew D., Rotter, Jerome I., Shyong Tai, E., Vilmundur, Gudnason, Vingerling, Johannes R., Siscovick, David S., Jie Jin Wang, Wong, Tien Y., Donnelly, P, Barroso, I, Blackwell, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, Hs, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Mathew, C, Mccarthy, Mi, Newton Cheh, C, Johnson, T, Gateva, V, Tobin, Md, Bochud, M, Coin, L, Najjar, Ss, Zhao, Jh, Heath, Sc, Eyheramendy, S, Papadakis, K, Voight, Bf, Scott, Lj, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, Jc, Khaw, Kt, Nilsson, P, van der Harst, P, Polidoro, Silvia, Grobbee, De, Onland Moret NC, Bots, Ml, Wain, Lv, Elliott, Ks, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, Pr, Hadley, D, Mcardle, Wl, Brown, M, Dominiczak, A, Newhouse, Sj, Samani, Nj, Webster, J, Zeggini, E, Beckmann, Js, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, Dm, Yuan, X, Groop, L, Orho Melander, M, Allione, A, Di Gregorio, A, Guarrera, Simonetta, Panico, S, Ricceri, Fulvio, Romanazzi, V, Sacerdote, Carlotta, Vineis, Paolo, Sandhu, Ms, Luben, Rn, Crawford, Gj, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, Ll, Collins, Fs, Jackson, Au, Mohlke, Kl, Stringham, Hm, Valle, Tt, Willer, Cj, Bergman, Rn, Morken, Ma, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, He, Kathiresan, S, Marrugat, J, O'Donnell, Cj, Schwartz, Sm, Siscovick, Ds, Subirana, I, Freimer, Nb, Hartikainen, Al, O'Reilly, Pf, Peltonen, L, Pouta, A, de Jong PE, Snieder, H, van Gilst WH, Clarke, R, Goel, A, Hamsten, A, Peden, Jf, Seedorf, U, Syvänen, Ac, Tognoni, G, Lakatta, Eg, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, Felix, Sb, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, U, Galan, P, Gut, Ig, Hercberg, S, Lathrop, Gm, Zeleneka, D, Soranzo, N, Williams, Fm, Zhai, G, Salomaa, V, Laakso, M, Elosua, R, Forouhi, Ng, Völzke, H, Uiterwaal, Cs, van der Schouw YT, Numans, Me, Matullo, Giuseppe, Navis, G, Berglund, G, Bingham, Sa, Kooner, Js, Connell, Jm, Bandinelli, S, Ferrucci, L, Watkins, H, Spector, Td, Tuomilehto, J, Altshuler, D, Strachan, Dp, Laan, M, Meneton, P, Wareham, Nj, Uda, M, Jarvelin, Mr, Mooser, V, Melander, O, Loos, Rj, Elliott, P, Abecasis, Gr, Caulfield, M, Munroe, P. B., Inouye, Michael [0000-0001-9413-6520], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Wellcome Trust Case Control Consortium 2, Global BPGen Consortium, Donnelly, P., Barroso, I., Blackwell, J.M., Bramon, E., Brown, M.A., Casas, J.P., Corvin, A., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H.S., Mathew, C.G., Palmer, C.N., Plomin, R., Rautanen, A., Sawcer, S.J., Trembath, R.C., Viswanathan, A.C., Wood, N.W., Spencer, C.C., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Giannoulatou, E., Pirinen, M., Pearson, R., Strange, A., Su, Z., Vukcevic, D., Langford, C., Hunt, S.E., Edkins, S., Gwilliam, R., Blackburn, H., Bumpstead, S.J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O.T., Liddle, J., Potter, S.C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Mathew, C., McCarthy, M.I., Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M.D., Bochud, M., Coin, L., Najjar, S.S., Zhao, J.H., Heath, S.C., Eyheramendy, S., Papadakis, K., Voight, B.F., Scott, L.J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J.C., Khaw, K.T., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D.E., Onland-Moret, N.C., Bots, M.L., Wain, L.V., Elliott, K.S., Teumer, A., Luan, J.J., Lucas, G., Kuusisto, J., Burton, P.R., Hadley, D., McArdle, W.L., Brown, M., Dominiczak, A., Newhouse, S.J., Samani, N.J., Webster, J., Zeggini, E., Beckmann, J.S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D.M., Yuan, X., Groop, L., Orho-Melander, M., Allione, A., Di Gregorio, A., Guarrera, S., Panico, S., Ricceri, F., Romanazzi, V., Sacerdote, C., Vineis, P., Sandhu, M.S., Luben, R.N., Crawford, G.J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L.L., Collins, F.S., Jackson, A.U., Mohlke, K.L., Stringham, H.M., Valle, T.T., Willer, C.J., Bergman, R.N., Morken, M.A., Döring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H.E., Kathiresan, S., Marrugat, J., O'Donnell, C.J., Schwartz, S.M., Siscovick, D.S., Subirana, I., Freimer, N.B., Hartikainen, A.L., O'Reilly, P.F., Peltonen, L., Pouta, A., de Jong, P.E., Snieder, H., van Gilst, W.H., Clarke, R., Goel, A., Hamsten, A., Peden, J.F., Seedorf, U., Syvänen, A.C., Tognoni, G., Lakatta, E.G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dörr, M., Ernst, F., Felix, S.B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Völker, U., Galan, P., Gut, I.G., Hercberg, S., Lathrop, G.M., Zeleneka, D., Soranzo, N., Williams, F.M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N.G., Völzke, H., Uiterwaal, C.S., van der Schouw, Y.T., Numans, M.E., Matullo, G., Navis, G., Berglund, G., Bingham, S.A., Kooner, J.S., Connell, J.M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T.D., Tuomilehto, J., Altshuler, D., Strachan, D.P., Laan, M., Meneton, P., Wareham, N.J., Uda, M., Jarvelin, M.R., Mooser, V., Melander, O., Loos, R.J., Elliott, P., Abecasis, G.R., Caulfield, M., Munroe, P.B., Ophthalmology, Epidemiology, Internal Medicine, Erasmus School of Social and Behavioural Sciences, and Obstetrics & Gynecology
Subjects: Male, Pathology, BLUE MOUNTAINS EYE, VESSEL DIAMETERS, lcsh:Medicine, MICROVASCULAR ABNORMALITIES, Genome-wide association study, Cardiovascular, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, genome-wide association, Microcirculation, Retinal Arteriolar Microcirculation, Myocardial infarction, lcsh:Science, Aged, 80 and over, Medicine(all), 0303 health sciences, Multidisciplinary, Agricultural and Biological Sciences(all), MEF2 Transcription Factors, Genomics, Middle Aged, 3. Good health, Arterioles, medicine.anatomical_structure, Medicine, Chromosomes, Human, Pair 5, Female, INCIDENT SEVERE HYPERTENSION, Research Article, medicine.medical_specialty, Genotype, Clinical Research Design, ANTIHYPERTENSIVE DRUG THERAPIES, Single-nucleotide polymorphism, White People, 03 medical and health sciences, Genome Analysis Tools, Vascular Biology, BEAVER DAM EYE, Genetics, Genome-Wide Association Studies, medicine, Humans, CORONARY-HEART-DISEASE, GENOME-WIDE ASSOCIATION, Biology, Aged, 030304 developmental biology, Retina, Models, Genetic, Biochemistry, Genetics and Molecular Biology(all), Vascular disease, business.industry, lcsh:R, Computational Biology, Retinal Vessels, Human Genetics, Retinal, medicine.disease, Ophthalmology, chemistry, Genetic Loci, VASCULAR CALIBER, 030221 ophthalmology & optometry, lcsh:Q, Meta-Analyses, GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK, business, Genome-Wide Association Study
Abstract: Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value -8. This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10-12 in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
Published: 2013
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45. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author: Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), Caulfield, M. (Mark), Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), and Caulfield, M. (Mark)
Published: 2014
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46. Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics

Author: Williams, SM, Giambartolomei, C, Vukcevic, D, Schadt, EE, Franke, L, Hingorani, AD, Wallace, C, Plagnol, V, Williams, SM, Giambartolomei, C, Vukcevic, D, Schadt, EE, Franke, L, Hingorani, AD, Wallace, C, and Plagnol, V
Abstract: Genetic association studies, in particular the genome-wide association study (GWAS) design, have provided a wealth of novel insights into the aetiology of a wide range of human diseases and traits, in particular cardiovascular diseases and lipid biomarkers. The next challenge consists of understanding the molecular basis of these associations. The integration of multiple association datasets, including gene expression datasets, can contribute to this goal. We have developed a novel statistical methodology to assess whether two association signals are consistent with a shared causal variant. An application is the integration of disease scans with expression quantitative trait locus (eQTL) studies, but any pair of GWAS datasets can be integrated in this framework. We demonstrate the value of the approach by re-analysing a gene expression dataset in 966 liver samples with a published meta-analysis of lipid traits including >100,000 individuals of European ancestry. Combining all lipid biomarkers, our re-analysis supported 26 out of 38 reported colocalisation results with eQTLs and identified 14 new colocalisation results, hence highlighting the value of a formal statistical test. In three cases of reported eQTL-lipid pairs (SYPL2, IFT172, TBKBP1) for which our analysis suggests that the eQTL pattern is not consistent with the lipid association, we identify alternative colocalisation results with SORT1, GCKR, and KPNB1, indicating that these genes are more likely to be causal in these genomic intervals. A key feature of the method is the ability to derive the output statistics from single SNP summary statistics, hence making it possible to perform systematic meta-analysis type comparisons across multiple GWAS datasets (implemented online at http://coloc.cs.ucl.ac.uk/coloc/). Our methodology provides information about candidate causal genes in associated intervals and has direct implications for the understanding of complex diseases as well as the design of drugs to targ
Published: 2014

47. The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Author: Davis, OSP, Band, G, Pirinen, M, Haworth, CMA, Meaburn, EL, Kovas, Y, Harlaar, N, Docherty, SJ, Hanscombe, KB, Trzaskowski, M, Curtis, CJC, Strange, A, Freeman, C, Bellenguez, C, Su, Z, Pearson, R, Vukcevic, D, Langford, C, Deloukas, P, Hunt, S, Gray, E, Dronov, S, Potter, SC, Tashakkori-Ghanbaria, A, Edkins, S, Bumpstead, SJ, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Duncanson, A, Jankowski, JAZ, Markus, HS, Mathew, CG, Palmer, CNA, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Barroso, I, Peltonen, L, Dale, PS, Petrill, SA, Schalkwyk, LS, Craig, IW, Lewis, CM, Price, TS, Donnelly, P, Plomin, R, Spencer, CCA, Davis, OSP, Band, G, Pirinen, M, Haworth, CMA, Meaburn, EL, Kovas, Y, Harlaar, N, Docherty, SJ, Hanscombe, KB, Trzaskowski, M, Curtis, CJC, Strange, A, Freeman, C, Bellenguez, C, Su, Z, Pearson, R, Vukcevic, D, Langford, C, Deloukas, P, Hunt, S, Gray, E, Dronov, S, Potter, SC, Tashakkori-Ghanbaria, A, Edkins, S, Bumpstead, SJ, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Duncanson, A, Jankowski, JAZ, Markus, HS, Mathew, CG, Palmer, CNA, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Barroso, I, Peltonen, L, Dale, PS, Petrill, SA, Schalkwyk, LS, Craig, IW, Lewis, CM, Price, TS, Donnelly, P, Plomin, R, and Spencer, CCA
Abstract: Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.
Published: 2014

48. The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism

Author: Klebe, S. (Stephan), Golmard, L. (Lisa), Nalls, M.A. (Michael), Saad, F. (Fred), Singleton, A. (Andrew), Bras, J. (Jose), Hardy, J. (John), Simón-Sánchez, J. (Javier), Heutink, P. (Peter), Kuhlenbäumer, G. (Gregor), Charfi, R. (Rim), Klein, C. (Christoph), Hagenah, J., Gasser, T. (Thomas), Wurster, K.D. (Kathrin), Lesage, S. (Suzanne), Lorenz, D. (Delia), Deuschl, G. (Günther), Durif, F. (Franck), Pollak, M.N. (Michael), Damier, P. (Philippe), Tison, F. (François), Durr, A., Amouyel, P. (Philippe), Lambert, J.C. (Jean Charles), Tzourio, C. (Christophe), Maubaret, C. (Cécilia), Charbonnier-Beaupel, F. (Fanny), Tahiri, K. (Khadija), Vidailhet, M. (M.), Martinez, M. (Maria), Brice, A., Corvol, J.C. (Jean-Christophe), Agid, Y. (Yves), Anheim, M. (M.), Bonnet, A.-M. (A.), Borg, M. (Michael), Broussolle, E. (E.), Corvol, J.C. (Jean Christophe), Damier, Ph. (Ph), Destée, A. (A.), Durif, F. (F.), Klebe, S. (S.), Lohmann, E. (E.), Penet, C. (C.), Krack, P. (P.), Rascol, O. (O.), Tison, F. (F.), Tranchant, C. (C.), Vérin, M. (M.), Viallet, F. (F.), Vidailhet, M. (Marie), Plagnol, V. (Vincent), Bras, J.M. (Jose), Hernandez, D.G. (Dena), Sharma, M., Sheerin, U.-M. (Una-Marie), Schulte, C. (Claudia), Sveinbjörnsdóttir, S. (Sigurlaug), Arepalli, S. (Sampath), Band, G. (Gavin), Vukcevic, D. (Damjan), Barker, R.A. (Roger), Bellinguez, C. (Céline), Ben-Shlomo, Y., Berendse, H.W. (Henk W.), Berg, D. (Daniela), Bhatia, K.P. (Kailash), Bie, R.M.A. (Rob) de, Biffi, A. (Alessandro), Bloem, B. (Bas), Bochdanovits, Z. (Zoltan), Bonin, M. (Malte) von, Brockmann, K., Brooks, J. (Janet), Burn, D.J. (David), Charlesworth, K. (Kate), Chen, H. (Honglei), Chinnery, P.F. (Patrick), Chong, S. (Sean), Clarke, C.E. (Carl), Cookson, M.R. (Mark), Cooper, J.M. (J. Mark), Counsell, C. (Carl), Dartigues, J.-F., Deloukas, P. (Panagiotis), Dexter, D.T. (David), Dijk, K.D. (Karin) van, Dillman, A. (Allissa), Durif, F. (Frank), Edkins, T. (Ted), Evans, J. (Jonathan Mark), Foltynie, T. (Thomas), Freeman, C. (Colin), Gao, J. (Jianjun), Gardner, M. (Mac), Gibbs, J. (Raphael), Goate, A.M. (Alison), Gray, E. (Emma), Guerreiro, R. (Rita), Gustafsson, O. (Omar), Harris, C. (Clare), Hellenthal, F.A., Hilten, J.J. (Jacobus) van, Hofman, A. (Albert), Hollenbeck, J.R. (John R.), Holton, J.L. (Janice), Hu, M. (Michele), Huang, X. (Xiaohong), Huber, H. (Heiko), Hudson, G. (Gavin), Hunt, S.E. (Sarah), Huttenlocher, J. (Johanna), Illig, T. (Thomas), Jónsson, P.V. (Pálmi), Langford, C. (Cordelia), Lees, A.J. (Andrew), Lichtner, P. (Peter), Limousin, P. (Patricia), Lopez, G., McNeill, N.H. (Nathan), Moorby, C. (Catriona), Moore, M. (Matt), Morris, H. (Huw), Morrison, K.E. (Karen), Mudanohwo, E. (Ese), O'Sullivan, S.S. (Sean), Pearson, J. (Justin), Pearson, R. (Ruth), Perlmutter, J.S. (Joel), Pétursson, H. (Hjörvar), Pirinen, M. (Matti), Post, B. (Bart), Ravina, B. (Bernard), Revesz, T. (Tamas), Riess, O. (Olaf), Rivadeneira Ramirez, F. (Fernando), Rizzu, P. (Patrizia), Ryten, M. (Mina), Sawcer, S.J. (Stephen), Schapira, A.H.V. (Anthony), Scheffer, H. (Hans), Shaw, K. (Karen), Shoulson, I. (Ira), Sidransky, E. (Ellen), Silva, R. (Rohan) de, Smith, C. (Colin), Spencer, C.C.A. (Chris C.), Stefansson, H. (Hreinn), Wolf, C. (Christiane), Stockton, J.D. (Joanna), Strange, A. (Amy), Su, Z. (Zhan), Talbot, D., Tanner, C.M. (Carlie), Tashakkori-Ghanbaria, A. (Avazeh), Trabzuni, D. (Danyah), Traynor, B.J. (Bryan), Uitterlinden, A.G. (André), Vandrovcova, J. (Jana), Velseboer, D. (Daan), Walker, R. (Robert), Warrenburg, B. (Bart) van de, Weale, M.E. (Michael), Wickremaratchi, M. (Mirdhu), Williams, N. (Nigel), Williams-Gray, C.H. (Caroline), Winder-Rhodes, S. (Sophie), Zwart, J-A. (John-Anker), Wood, N.W. (Nicholas), Klebe, S. (Stephan), Golmard, L. (Lisa), Nalls, M.A. (Michael), Saad, F. (Fred), Singleton, A. (Andrew), Bras, J. (Jose), Hardy, J. (John), Simón-Sánchez, J. (Javier), Heutink, P. (Peter), Kuhlenbäumer, G. (Gregor), Charfi, R. (Rim), Klein, C. (Christoph), Hagenah, J., Gasser, T. (Thomas), Wurster, K.D. (Kathrin), Lesage, S. (Suzanne), Lorenz, D. (Delia), Deuschl, G. (Günther), Durif, F. (Franck), Pollak, M.N. (Michael), Damier, P. (Philippe), Tison, F. (François), Durr, A., Amouyel, P. (Philippe), Lambert, J.C. (Jean Charles), Tzourio, C. (Christophe), Maubaret, C. (Cécilia), Charbonnier-Beaupel, F. (Fanny), Tahiri, K. (Khadija), Vidailhet, M. (M.), Martinez, M. (Maria), Brice, A., Corvol, J.C. (Jean-Christophe), Agid, Y. (Yves), Anheim, M. (M.), Bonnet, A.-M. (A.), Borg, M. (Michael), Broussolle, E. (E.), Corvol, J.C. (Jean Christophe), Damier, Ph. (Ph), Destée, A. (A.), Durif, F. (F.), Klebe, S. (S.), Lohmann, E. (E.), Penet, C. (C.), Krack, P. (P.), Rascol, O. (O.), Tison, F. (F.), Tranchant, C. (C.), Vérin, M. (M.), Viallet, F. (F.), Vidailhet, M. (Marie), Plagnol, V. (Vincent), Bras, J.M. (Jose), Hernandez, D.G. (Dena), Sharma, M., Sheerin, U.-M. (Una-Marie), Schulte, C. (Claudia), Sveinbjörnsdóttir, S. (Sigurlaug), Arepalli, S. (Sampath), Band, G. (Gavin), Vukcevic, D. (Damjan), Barker, R.A. (Roger), Bellinguez, C. (Céline), Ben-Shlomo, Y., Berendse, H.W. (Henk W.), Berg, D. (Daniela), Bhatia, K.P. (Kailash), Bie, R.M.A. (Rob) de, Biffi, A. (Alessandro), Bloem, B. (Bas), Bochdanovits, Z. (Zoltan), Bonin, M. (Malte) von, Brockmann, K., Brooks, J. (Janet), Burn, D.J. (David), Charlesworth, K. (Kate), Chen, H. (Honglei), Chinnery, P.F. (Patrick), Chong, S. (Sean), Clarke, C.E. (Carl), Cookson, M.R. (Mark), Cooper, J.M. (J. Mark), Counsell, C. (Carl), Dartigues, J.-F., Deloukas, P. (Panagiotis), Dexter, D.T. (David), Dijk, K.D. (Karin) van, Dillman, A. (Allissa), Durif, F. (Frank), Edkins, T. (Ted), Evans, J. (Jonathan Mark), Foltynie, T. (Thomas), Freeman, C. (Colin), Gao, J. (Jianjun), Gardner, M. (Mac), Gibbs, J. (Raphael), Goate, A.M. (Alison), Gray, E. (Emma), Guerreiro, R. (Rita), Gustafsson, O. (Omar), Harris, C. (Clare), Hellenthal, F.A., Hilten, J.J. (Jacobus) van, Hofman, A. (Albert), Hollenbeck, J.R. (John R.), Holton, J.L. (Janice), Hu, M. (Michele), Huang, X. (Xiaohong), Huber, H. (Heiko), Hudson, G. (Gavin), Hunt, S.E. (Sarah), Huttenlocher, J. (Johanna), Illig, T. (Thomas), Jónsson, P.V. (Pálmi), Langford, C. (Cordelia), Lees, A.J. (Andrew), Lichtner, P. (Peter), Limousin, P. (Patricia), Lopez, G., McNeill, N.H. (Nathan), Moorby, C. (Catriona), Moore, M. (Matt), Morris, H. (Huw), Morrison, K.E. (Karen), Mudanohwo, E. (Ese), O'Sullivan, S.S. (Sean), Pearson, J. (Justin), Pearson, R. (Ruth), Perlmutter, J.S. (Joel), Pétursson, H. (Hjörvar), Pirinen, M. (Matti), Post, B. (Bart), Ravina, B. (Bernard), Revesz, T. (Tamas), Riess, O. (Olaf), Rivadeneira Ramirez, F. (Fernando), Rizzu, P. (Patrizia), Ryten, M. (Mina), Sawcer, S.J. (Stephen), Schapira, A.H.V. (Anthony), Scheffer, H. (Hans), Shaw, K. (Karen), Shoulson, I. (Ira), Sidransky, E. (Ellen), Silva, R. (Rohan) de, Smith, C. (Colin), Spencer, C.C.A. (Chris C.), Stefansson, H. (Hreinn), Wolf, C. (Christiane), Stockton, J.D. (Joanna), Strange, A. (Amy), Su, Z. (Zhan), Talbot, D., Tanner, C.M. (Carlie), Tashakkori-Ghanbaria, A. (Avazeh), Trabzuni, D. (Danyah), Traynor, B.J. (Bryan), Uitterlinden, A.G. (André), Vandrovcova, J. (Jana), Velseboer, D. (Daan), Walker, R. (Robert), Warrenburg, B. (Bart) van de, Weale, M.E. (Michael), Wickremaratchi, M. (Mirdhu), Williams, N. (Nigel), Williams-Gray, C.H. (Caroline), Winder-Rhodes, S. (Sophie), Zwart, J-A. (John-Anker), and Wood, N.W. (Nicholas)
Abstract: The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson’s disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polym
Published: 2013
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49. Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

Author: Strange, A., Bellenguez, C., Sim, X., Luben, R., Hysi, P. G., Ramdas, W. D., van Koolwijk, L. M. E., Freeman, C., Pirinen, M., Su, Z., Band, G., Pearson, R., Vukcevic, D., Langford, C., Deloukas, P., Hunt, S., Gray, E., Dronov, S., Potter, S. C., Tashakkori-Ghanbaria, A., Edkins, S., Bumpstead, S. J., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Duncanson, A., Jankowski, Janusz, Markus, H. S., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Wood, N. W., Barroso, I., Peltonen, L., Healey, P., McGuffin, P., Topouzis, F., Klaver, C. C. W., van Duijn, C. M., Mackey, D. A., Young, T. L., Hammond, C. J., Khaw, K.-T., Wareham, N., Wang, J. J., Wong, T. Y., Foster, P. J., Mitchell, P., Spencer, C. C. A., Donnelly, P., Viswanathan, A. C., Strange, A., Bellenguez, C., Sim, X., Luben, R., Hysi, P. G., Ramdas, W. D., van Koolwijk, L. M. E., Freeman, C., Pirinen, M., Su, Z., Band, G., Pearson, R., Vukcevic, D., Langford, C., Deloukas, P., Hunt, S., Gray, E., Dronov, S., Potter, S. C., Tashakkori-Ghanbaria, A., Edkins, S., Bumpstead, S. J., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Duncanson, A., Jankowski, Janusz, Markus, H. S., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Wood, N. W., Barroso, I., Peltonen, L., Healey, P., McGuffin, P., Topouzis, F., Klaver, C. C. W., van Duijn, C. M., Mackey, D. A., Young, T. L., Hammond, C. J., Khaw, K.-T., Wareham, N., Wang, J. J., Wong, T. Y., Foster, P. J., Mitchell, P., Spencer, C. C. A., Donnelly, P., and Viswanathan, A. C.
Abstract: To discover quantitative trait loci for intraocular pressure, a major risk factor for glaucoma and the only modifiable one, we performed a genome-wide association study on a discovery cohort of 2175 individuals from Sydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10−8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30–0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.
Published: 2013

50. Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

Author: Fakiola, M, Strange, A, Cordell, HJ, Miller, EN, Pirinen, M, Su, Z, Mishra, A, Mehrotra, S, Monteiro, GR, Band, G, Bellenguez, C, Dronov, S, Edkins, S, Freeman, C, Giannoulatou, E, Gray, E, Hunt, SE, Lacerda, HG, Langford, C, Pearson, R, Pontes, NN, Rai, M, Singh, SP, Smith, L, Sousa, O, Vukcevic, D, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Wilson, ME, Deloukas, P, Peltonen, L, Christiansen, F, Witt, C, Jeronimo, SMB, Sundar, S, Spencer, CCA, Blackwell, JM, Donnelly, P, Fakiola, M, Strange, A, Cordell, HJ, Miller, EN, Pirinen, M, Su, Z, Mishra, A, Mehrotra, S, Monteiro, GR, Band, G, Bellenguez, C, Dronov, S, Edkins, S, Freeman, C, Giannoulatou, E, Gray, E, Hunt, SE, Lacerda, HG, Langford, C, Pearson, R, Pontes, NN, Rai, M, Singh, SP, Smith, L, Sousa, O, Vukcevic, D, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Wilson, ME, Deloukas, P, Peltonen, L, Christiansen, F, Witt, C, Jeronimo, SMB, Sundar, S, Spencer, CCA, Blackwell, JM, and Donnelly, P
Abstract: To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P(combined) = 2.76 × 10(-17) and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.
Published: 2013

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