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

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1. Assessment of network module identification across complex diseases

Author: Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Marbach, D, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, W, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Choobdar S., Ahsen M. E., Crawford J., Tomasoni M., Fang T., Lamparter D., Lin J., Hescott B., Hu X., Mercer J., Natoli T., Narayan R., Aicheler F., Amoroso N., Arenas A., Azhagesan K., Baker A., Banf M., Batzoglou S., Baudot A., Bellotti R., Bergmann S., Boroevich K. A., Brun C., Cai S., Caldera M., Calderone A., Cesareni G., Chen W., Chichester C., Cowen L., Cui H., Dao P., De Domenico M., Dhroso A., Didier G., Divine M., del Sol A., Feng X., Flores-Canales J. C., Fortunato S., Gitter A., Gorska A., Guan Y., Guenoche A., Gomez S., Hamza H., Hartmann A., He S., Heijs A., Heinrich J., Hu Y., Huang X., Hughitt V. K., Jeon M., Jeub L., Johnson N. T., Joo K., Joung I. S., Jung S., Kalko S. G., Kamola P. J., Kang J., Kaveelerdpotjana B., Kim M., Kim Y. -A., Kohlbacher O., Korkin D., Krzysztof K., Kunji K., Kutalik Z., Lage K., Lang-Brown S., Le T. D., Lee J., Lee S., Li D., Li J., Liu L., Loizou A., Luo Z., Lysenko A., Ma T., Mall R., Marbach D., Mattia T., Medvedovic M., Menche J., Micarelli E., Monaco A., Muller F., Narykov O., Norman T., Park S., Perfetto L., Perrin D., Pirro S., Przytycka T. M., Qian X., Raman K., Ramazzotti D., Ramsahai E., Ravindran B., Rennert P., Saez-Rodriguez J., Scharfe C., Sharan R., Shi N., Shin W., Shu H., Sinha H., Slonim D. K., Spinelli L., Srinivasan S., Subramanian A., Suver C., Szklarczyk D., Tangaro S., Thiagarajan S., Tichit L., Tiede T., Tripathi B., Tsherniak A., Tsunoda T., Turei D., Ullah E., Vahedi G., Valdeolivas A., Vivek J., von Mering C., Waagmeester A., Wang B., Wang Y., Weir B. A., White S., Winkler S., Xu K., Xu T., Yan C., Yang L., Yu K., Yu X., Zaffaroni G., Zaslavskiy M., Zeng T., Zhang J. D., Zhang L., Zhang W., Zhang X., Zhang J., Zhou X., Zhou J., Zhu H., Zhu J., Zuccon G., Stolovitzky G., Cowen L. J., Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Marbach, D, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, W, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Choobdar S., Ahsen M. E., Crawford J., Tomasoni M., Fang T., Lamparter D., Lin J., Hescott B., Hu X., Mercer J., Natoli T., Narayan R., Aicheler F., Amoroso N., Arenas A., Azhagesan K., Baker A., Banf M., Batzoglou S., Baudot A., Bellotti R., Bergmann S., Boroevich K. A., Brun C., Cai S., Caldera M., Calderone A., Cesareni G., Chen W., Chichester C., Cowen L., Cui H., Dao P., De Domenico M., Dhroso A., Didier G., Divine M., del Sol A., Feng X., Flores-Canales J. C., Fortunato S., Gitter A., Gorska A., Guan Y., Guenoche A., Gomez S., Hamza H., Hartmann A., He S., Heijs A., Heinrich J., Hu Y., Huang X., Hughitt V. K., Jeon M., Jeub L., Johnson N. T., Joo K., Joung I. S., Jung S., Kalko S. G., Kamola P. J., Kang J., Kaveelerdpotjana B., Kim M., Kim Y. -A., Kohlbacher O., Korkin D., Krzysztof K., Kunji K., Kutalik Z., Lage K., Lang-Brown S., Le T. D., Lee J., Lee S., Li D., Li J., Liu L., Loizou A., Luo Z., Lysenko A., Ma T., Mall R., Marbach D., Mattia T., Medvedovic M., Menche J., Micarelli E., Monaco A., Muller F., Narykov O., Norman T., Park S., Perfetto L., Perrin D., Pirro S., Przytycka T. M., Qian X., Raman K., Ramazzotti D., Ramsahai E., Ravindran B., Rennert P., Saez-Rodriguez J., Scharfe C., Sharan R., Shi N., Shin W., Shu H., Sinha H., Slonim D. K., Spinelli L., Srinivasan S., Subramanian A., Suver C., Szklarczyk D., Tangaro S., Thiagarajan S., Tichit L., Tiede T., Tripathi B., Tsherniak A., Tsunoda T., Turei D., Ullah E., Vahedi G., Valdeolivas A., Vivek J., von Mering C., Waagmeester A., Wang B., Wang Y., Weir B. A., White S., Winkler S., Xu K., Xu T., Yan C., Yang L., Yu K., Yu X., Zaffaroni G., Zaslavskiy M., Zeng T., Zhang J. D., Zhang L., Zhang W., Zhang X., Zhang J., Zhou X., Zhou J., Zhu H., Zhu J., Zuccon G., Stolovitzky G., and Cowen L. J.
Abstract: Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the ‘Disease Module Identification DREAM Challenge’, an open competition to comprehensively assess module identification methods across diverse protein–protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.
Published: 2019

2. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (Nature Genetics, (2018), 50, 1, (26-41), 10.1038/s41588-017-0011-x)

Author: Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., Guo, X., Hendricks, A. E., Karaderi, T., Lempradl, A., Locke, A. E., Mahajan, A., Marouli, E., Sivapalaratnam, S., Young, K. L., Alfred, T., Feitosa, M. F., Masca, N. G. D., Manning, A. K., Medina-Gomez, C., Mudgal, P., M. C. Y., Ng, Reiner, A. P., Vedantam, S., Willems, S. M., Winkler, T. W., Abecasis, G., Aben, K. K., Alam, D. S., Alharthi, S. E., Marchiori, Allison, Amouyel, P., Asselbergs, F. W., Auer, P. L., Balkau, B., Bang, L. E., Barroso, I., Bastarache, L., Benn, M., Bergmann, S., Bielak, L. F., Bluher, M., Boehnke, M., Boeing, H., Boerwinkle, E., Boger, C. A., Bork-Jensen, J., Bots, M. L., Bottinger, E. P., Bowden, D. W., Brandslund, I., Breen, G., Brilliant, M. H., Broer, L., Brumat, M., Burt, A. A., Butterworth, A. S., Campbell, P. T., Cappellani, S., Carey, D. J., Catamo, E., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Chowdhury, R., Christensen, C., Chu, A. Y., Cocca, M., Collins, F. S., Cook, J. P., Corley, J., Galbany, J. C., Cox, A. J., Crosslin, D. S., Cuellar-Partida, G., D'Eustacchio, A., Danesh, J., Davies, G., Bakker, P. I. W., Groot, M. C. H., Mutsert, R., Deary, I. J., Dedoussis, G., Demerath, E. W., Heijer, M., Hollander, A. I., Ruijter, H. M., Dennis, J. G., Denny, J. C., Di Angelantonio, E., Drenos, F., Du, M., Dube, M. -P., Dunning, A. M., Easton, D. F., Edwards, T. L., Ellinghaus, D., Ellinor, P. T., Elliott, P., Evangelou, E., Farmaki, A. -E., Farooqi, I. S., Faul, J. D., Fauser, S., Feng, S., Ferrannini, E., Ferrieres, J., Florez, J. C., Ford, I., Fornage, M., Franco, O. H., Franke, A., Franks, P. W., Friedrich, N., Frikke-Schmidt, R., Galesloot, T. E., Gan, W., Gandin, I., Gasparini, P., Gibson, J., Giedraitis, V., Gjesing, A. P., Gordon-Larsen, P., Gorski, M., Grabe, H. -J., Grant, S. F. A., Grarup, N., Griffiths, H. L., Grove, M. L., Gudnason, V., Gustafsson, S., Haessler, J., Hakonarson, H., Hammerschlag, A. R., Hansen, T., Harris, K. M., Harris, T. B., Hattersley, A. T., Have, C. T., Hayward, C., He, L., Heard-Costa, N. L., Heath, A. C., Heid, I. M., Helgeland, O., Hernesniemi, J., Hewitt, A. W., Holmen, O. L., Hovingh, G. K., Howson, J. M. M., Hu, Y., Huang, P. L., Huffman, J. E., Ikram, M. A., Ingelsson, E., Jackson, A. U., Jansson, J. -H., Jarvik, G. P., Jensen, G. B., Jia, Y., Johansson, S., Jorgensen, M. E., Jorgensen, T., Jukema, J. W., Kahali, B., Kahn, R. S., Kahonen, M., Kamstrup, P. R., Kanoni, S., Kaprio, J., Karaleftheri, M., Kardia, S. L. R., Karpe, F., Kathiresan, S., Kee, F., Kiemeney, L. A., Kim, E., Kitajima, H., Komulainen, P., Kooner, J. S., Kooperberg, C., Korhonen, T., Kovacs, P., Kuivaniemi, H., Kutalik, Z., Kuulasmaa, K., Kuusisto, J., Laakso, M., Lakka, T. A., Lamparter, D., Lange, E. M., Lange, L. A., Langenberg, C., Larson, E. B., Lee, N. R., Lehtimaki, T., Lewis, C. E., Li, H., Li, J., Li-Gao, R., Lin, H., Lin, K. -H., Lin, L. -A., Lin, X., Lind, L., Lindstrom, J., Linneberg, A., Liu, C. -T., Liu, D. J., Liu, Y., K. S., Lo, Lophatananon, A., Lotery, A. J., Loukola, A., Luan, J., Lubitz, S. A., Lyytikainen, L. -P., Mannisto, S., Marenne, G., Mazul, A. L., Mccarthy, M. I., McKean-Cowdin, R., Medland, S. E., Meidtner, K., Milani, L., Mistry, V., Mitchell, P., Mohlke, K. L., Moilanen, L., Moitry, M., Montgomery, G. W., Mook-Kanamori, D. O., Moore, C., Mori, T. A., Morris, A. D., Morris, A. P., Muller-Nurasyid, M., Munroe, P. B., Nalls, M. A., Narisu, N., Nelson, C. P., Neville, M., Nielsen, S. F., Nikus, K., Njolstad, P. R., Nordestgaard, B. G., Nyholt, D. R., O'Connel, J. R., O'Donoghue, M. L., Loohuis, L. M. O., Ophoff, R. A., Owen, K. R., Packard, C. J., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pasterkamp, G., Patel, A. P., Pattie, A., Pedersen, O., Peissig, P. L., Peloso, G. M., Pennell, C. E., Perola, M., Perry, J. A., Perry, J. R. B., Pers, T. H., Person, T. N., Peters, A., Petersen, E. R. B., Peyser, P. A., Pirie, A., Polasek, O., Polderman, T. J., Puolijoki, H., Raitakari, O. T., Rasheed, A., Rauramaa, R., Reilly, D. F., Renstrom, F., Rheinberger, M., Ridker, P. M., Rioux, J. D., Rivas, M. A., Roberts, D. J., Robertson, N. R., Robino, A., Rolandsson, O., Rudan, I., Ruth, K. S., Saleheen, D., Salomaa, V., Samani, N. J., Sapkota, Y., Sattar, N., Schoen, R. E., Schreiner, P. J., Schulze, M. B., Scott, R. A., Segura-Lepe, M. P., Shah, S. H., Sheu, W. H. -H., Sim, X., Slater, A. J., Small, K. S., Smith, A. V., Southam, L., Spector, T. D., Speliotes, E. K., Starr, J. M., Stefansson, K., Steinthorsdottir, V., Stirrups, K. E., Strauch, K., Stringham, H. M., Stumvoll, M., Sun, L., Surendran, P., Swift, A. J., Tada, H., Tansey, K. E., Tardif, J. -C., Taylor, K. D., Teumer, A., Thompson, D. J., Thorleifsson, G., Thorsteinsdottir, U., Thuesen, B. H., Tonjes, A., Tromp, G., Trompet, S., Tsafantakis, E., Tuomilehto, J., Tybjaerg-Hansen, A., Tyrer, J. P., Uher, R., Uitterlinden, A. G., Uusitupa, M., Laan, S. W., Duijn, C. M., Leeuwen, N., van Setten, J., Vanhala, M., Varbo, A., Varga, T. V., Varma, R., Edwards, D. R. V., Vermeulen, S. H., Veronesi, G., Vestergaard, H., Vitart, V., Vogt, T. F., Volker, U., Vuckovic, D., Wagenknecht, L. E., Walker, M., Wallentin, L., Wang, F., Wang, C. A., Wang, S., Wang, Y., Ware, E. B., Wareham, N. J., Warren, H. R., Waterworth, D. M., Wessel, J., White, H. D., Willer, C. J., Wilson, J. G., Witte, D. R., Wood, A. R., Wu, Y., Yaghootkar, H., Yao, J., Yao, P., Yerges-Armstrong, L. M., Young, R., Zeggini, E., Zhan, X., Zhang, W., Zhao, J. H., Zhao, W., Zhou, W., Zondervan, K. T., Rotter, J. I., Pospisilik, J. A., Rivadeneira, F., Borecki, I. B., Deloukas, P., Frayling, T. M., Lettre, G., North, K. E., Lindgren, C. M., Hirschhorn, J. N., Loos, R. J. F., Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., Guo, X., Hendricks, A. E., Karaderi, T., Lempradl, A., Locke, A. E., Mahajan, A., Marouli, E., Sivapalaratnam, S., Young, K. L., Alfred, T., Feitosa, M. F., Masca, N. G. D., Manning, A. K., Medina-Gomez, C., Mudgal, P., Ng, M. C. Y., Reiner, A. P., Vedantam, S., Willems, S. M., Winkler, T. W., Abecasis, G., Aben, K. K., Alam, D. S., Alharthi, S. E., Marchiori, Allison, Amouyel, P., Asselbergs, F. W., Auer, P. L., Balkau, B., Bang, L. E., Barroso, I., Bastarache, L., Benn, M., Bergmann, S., Bielak, L. F., Bluher, M., Boehnke, M., Boeing, H., Boerwinkle, E., Boger, C. A., Bork-Jensen, J., Bots, M. L., Bottinger, E. P., Bowden, D. W., Brandslund, I., Breen, G., Brilliant, M. H., Broer, L., Brumat, M., Burt, A. A., Butterworth, A. S., Campbell, P. T., Cappellani, S., Carey, D. J., Catamo, E., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Chowdhury, R., Christensen, C., Chu, A. Y., Cocca, M., Collins, F. S., Cook, J. P., Corley, J., Galbany, J. C., Cox, A. J., Crosslin, D. S., Cuellar-Partida, G., D'Eustacchio, A., Danesh, J., Davies, G., Bakker, P. I. W., Groot, M. C. H., Mutsert, R., Deary, I. J., Dedoussis, G., Demerath, E. W., Heijer, M., Hollander, A. I., Ruijter, H. M., Dennis, J. G., Denny, J. C., Di Angelantonio, E., Drenos, F., Du, M., Dube, M. -P., Dunning, A. M., Easton, D. F., Edwards, T. L., Ellinghaus, D., Ellinor, P. T., Elliott, P., Evangelou, E., Farmaki, A. -E., Farooqi, I. S., Faul, J. D., Fauser, S., Feng, S., Ferrannini, E., Ferrieres, J., Florez, J. C., Ford, I., Fornage, M., Franco, O. H., Franke, A., Franks, P. W., Friedrich, N., Frikke-Schmidt, R., Galesloot, T. E., Gan, W., Gandin, I., Gasparini, P., Gibson, J., Giedraitis, V., Gjesing, A. P., Gordon-Larsen, P., Gorski, M., Grabe, H. -J., Grant, S. F. A., Grarup, N., Griffiths, H. L., Grove, M. L., Gudnason, V., Gustafsson, S., Haessler, J., Hakonarson, H., Hammerschlag, A. R., Hansen, T., Harris, K. M., Harris, T. B., Hattersley, A. T., Have, C. T., Hayward, C., He, L., Heard-Costa, N. L., Heath, A. C., Heid, I. M., Helgeland, O., Hernesniemi, J., Hewitt, A. W., Holmen, O. L., Hovingh, G. K., Howson, J. M. M., Hu, Y., Huang, P. L., Huffman, J. E., Ikram, M. A., Ingelsson, E., Jackson, A. U., Jansson, J. -H., Jarvik, G. P., Jensen, G. B., Jia, Y., Johansson, S., Jorgensen, M. E., Jorgensen, T., Jukema, J. W., Kahali, B., Kahn, R. S., Kahonen, M., Kamstrup, P. R., Kanoni, S., Kaprio, J., Karaleftheri, M., Kardia, S. L. R., Karpe, F., Kathiresan, S., Kee, F., Kiemeney, L. A., Kim, E., Kitajima, H., Komulainen, P., Kooner, J. S., Kooperberg, C., Korhonen, T., Kovacs, P., Kuivaniemi, H., Kutalik, Z., Kuulasmaa, K., Kuusisto, J., Laakso, M., Lakka, T. A., Lamparter, D., Lange, E. M., Lange, L. A., Langenberg, C., Larson, E. B., Lee, N. R., Lehtimaki, T., Lewis, C. E., Li, H., Li, J., Li-Gao, R., Lin, H., Lin, K. -H., Lin, L. -A., Lin, X., Lind, L., Lindstrom, J., Linneberg, A., Liu, C. -T., Liu, D. J., Liu, Y., Lo, K. S., Lophatananon, A., Lotery, A. J., Loukola, A., Luan, J., Lubitz, S. A., Lyytikainen, L. -P., Mannisto, S., Marenne, G., Mazul, A. L., Mccarthy, M. I., McKean-Cowdin, R., Medland, S. E., Meidtner, K., Milani, L., Mistry, V., Mitchell, P., Mohlke, K. L., Moilanen, L., Moitry, M., Montgomery, G. W., Mook-Kanamori, D. O., Moore, C., Mori, T. A., Morris, A. D., Morris, A. P., Muller-Nurasyid, M., Munroe, P. B., Nalls, M. A., Narisu, N., Nelson, C. P., Neville, M., Nielsen, S. F., Nikus, K., Njolstad, P. R., Nordestgaard, B. G., Nyholt, D. R., O'Connel, J. R., O'Donoghue, M. L., Loohuis, L. M. O., Ophoff, R. A., Owen, K. R., Packard, C. J., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pasterkamp, G., Patel, A. P., Pattie, A., Pedersen, O., Peissig, P. L., Peloso, G. M., Pennell, C. E., Perola, M., Perry, J. A., Perry, J. R. B., Pers, T. H., Person, T. N., Peters, A., Petersen, E. R. B., Peyser, P. A., Pirie, A., Polasek, O., Polderman, T. J., Puolijoki, H., Raitakari, O. T., Rasheed, A., Rauramaa, R., Reilly, D. F., Renstrom, F., Rheinberger, M., Ridker, P. M., Rioux, J. D., Rivas, M. A., Roberts, D. J., Robertson, N. R., Robino, A., Rolandsson, O., Rudan, I., Ruth, K. S., Saleheen, D., Salomaa, V., Samani, N. J., Sapkota, Y., Sattar, N., Schoen, R. E., Schreiner, P. J., Schulze, M. B., Scott, R. A., Segura-Lepe, M. P., Shah, S. H., Sheu, W. H. -H., Sim, X., Slater, A. J., Small, K. S., Smith, A. V., Southam, L., Spector, T. D., Speliotes, E. K., Starr, J. M., Stefansson, K., Steinthorsdottir, V., Stirrups, K. E., Strauch, K., Stringham, H. M., Stumvoll, M., Sun, L., Surendran, P., Swift, A. J., Tada, H., Tansey, K. E., Tardif, J. -C., Taylor, K. D., Teumer, A., Thompson, D. J., Thorleifsson, G., Thorsteinsdottir, U., Thuesen, B. H., Tonjes, A., Tromp, G., Trompet, S., Tsafantakis, E., Tuomilehto, J., Tybjaerg-Hansen, A., Tyrer, J. P., Uher, R., Uitterlinden, A. G., Uusitupa, M., Laan, S. W., Duijn, C. M., Leeuwen, N., van Setten, J., Vanhala, M., Varbo, A., Varga, T. V., Varma, R., Edwards, D. R. V., Vermeulen, S. H., Veronesi, G., Vestergaard, H., Vitart, V., Vogt, T. F., Volker, U., Vuckovic, D., Wagenknecht, L. E., Walker, M., Wallentin, L., Wang, F., Wang, C. A., Wang, S., Wang, Y., Ware, E. B., Wareham, N. J., Warren, H. R., Waterworth, D. M., Wessel, J., White, H. D., Willer, C. J., Wilson, J. G., Witte, D. R., Wood, A. R., Wu, Y., Yaghootkar, H., Yao, J., Yao, P., Yerges-Armstrong, L. M., Young, R., Zeggini, E., Zhan, X., Zhang, W., Zhao, J. H., Zhao, W., Zhou, W., Zondervan, K. T., Rotter, J. I., Pospisilik, J. A., Rivadeneira, F., Borecki, I. B., Deloukas, P., Frayling, T. M., Lettre, G., North, K. E., Lindgren, C. M., Hirschhorn, J. N., and Loos, R. J. F.
Subjects: Publisher correction
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019

3. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

4. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

5. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

Author: Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., Baaij, J.H.F. de, Belge, H., Nagele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., Ulivi, S., Rueedi, R., Lamparter, D., Mace, A., Sala, C., Lenarduzzi, S., Ponte, B., Pruijm, M., Ackermann, D., Ehret, G., Baptista, D., Polasek, O., Rudan, I., Hurd, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., Devuyst, O., Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., Baaij, J.H.F. de, Belge, H., Nagele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., Ulivi, S., Rueedi, R., Lamparter, D., Mace, A., Sala, C., Lenarduzzi, S., Ponte, B., Pruijm, M., Ackermann, D., Ehret, G., Baptista, D., Polasek, O., Rudan, I., Hurd, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., and Devuyst, O.
Abstract: 1 januari 2018, Contains fulltext : 184156.pdf (publisher's version ) (Closed access), Magnesium (Mg(2+)) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg(2+), which is crucial for Mg(2+) homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg(2+) homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4x10(-13)) near TRPM6, which encodes an epithelial Mg(2+) channel, and rs35929 (P=2.1x10(-11)), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg(2+) regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg(2+) wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg(2+) deficiency to insulin resistance and obesity.
Published: 2018

6. Rare and low-frequency coding variants alter human adult height

Author: Marouli, E., Graff, M, Medina-Gomez, C., Lo, K.S., Wood, A.R., Kjaer, T.R., Fine, R.S., Lu, Y., Schurmann, C., Highland, H.M., Rueger, S., Thorleifsson, G., Justice, A.E., Lamparter, D., Stirrups, K.E., Turcot, V., Young, K.L., Winkler, T.W., Esko, T., Karaderi, T., Locke, A.E., Masca, N.G., Ng, M.C., Mudgal, P., Rivas, M.A., Vedantam, S., Mahajan, A., Guo, X., Abecasis, G., Aben, K.K.H., Adair, L.S., Alam, D.S., Albrecht, E., Allin, K.H., Allison, M., Amouyel, P., Appel, E.V., Arveiler, D., Asselbergs, F.W., Auer, P.L., Balkau, B., Banas, B., Bang, L.E., Benn, M., Bergmann, S., Bielak, L.F., Bluher, M., Boeing, H., Boerwinkle, E., Boger, C.A., Bonnycastle, L.L., Bork-Jensen, J., Bots, M.L., Bottinger, E.P., Bowden, D.W., Brandslund, I., Breen, G., Brilliant, M.H., Broer, L., Burt, A.A., Butterworth, A.S., Carey, D.J., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Chen, Y.I., Chowdhury, R., Christensen, C., Chu, A.Y., Cocca, M., Collins, F.S., Cook, J.P., Corley, J., Galbany, J.C., Cox, A.J., Cuellar-Partida, G., Danesh, J., Davies, G., Bakker, P.I. de, Borst, G.J. de, Denus, S. de, Groot, M.C. de, Mutsert, R. de, Deary, I.J., Dedoussis, G., Demerath, E.W., Hollander, A.I. den, Dennis, J.G., Angelantonio, E. Di, Drenos, F., Du, M., Dunning, A.M., Easton, D.F., Ebeling, T., Edwards, T.L., Ellinor, P.T., Elliott, P., Evangelou, E., Farmaki, A.E., Faul, J.D., Galesloot, T.E., Kiemeney, L.A., Kluivers, K.B., Vermeulen, S.H., Corominas-Galbany, J., Hoyng, C.B., et al., Marouli, E., Graff, M, Medina-Gomez, C., Lo, K.S., Wood, A.R., Kjaer, T.R., Fine, R.S., Lu, Y., Schurmann, C., Highland, H.M., Rueger, S., Thorleifsson, G., Justice, A.E., Lamparter, D., Stirrups, K.E., Turcot, V., Young, K.L., Winkler, T.W., Esko, T., Karaderi, T., Locke, A.E., Masca, N.G., Ng, M.C., Mudgal, P., Rivas, M.A., Vedantam, S., Mahajan, A., Guo, X., Abecasis, G., Aben, K.K.H., Adair, L.S., Alam, D.S., Albrecht, E., Allin, K.H., Allison, M., Amouyel, P., Appel, E.V., Arveiler, D., Asselbergs, F.W., Auer, P.L., Balkau, B., Banas, B., Bang, L.E., Benn, M., Bergmann, S., Bielak, L.F., Bluher, M., Boeing, H., Boerwinkle, E., Boger, C.A., Bonnycastle, L.L., Bork-Jensen, J., Bots, M.L., Bottinger, E.P., Bowden, D.W., Brandslund, I., Breen, G., Brilliant, M.H., Broer, L., Burt, A.A., Butterworth, A.S., Carey, D.J., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Chen, Y.I., Chowdhury, R., Christensen, C., Chu, A.Y., Cocca, M., Collins, F.S., Cook, J.P., Corley, J., Galbany, J.C., Cox, A.J., Cuellar-Partida, G., Danesh, J., Davies, G., Bakker, P.I. de, Borst, G.J. de, Denus, S. de, Groot, M.C. de, Mutsert, R. de, Deary, I.J., Dedoussis, G., Demerath, E.W., Hollander, A.I. den, Dennis, J.G., Angelantonio, E. Di, Drenos, F., Du, M., Dunning, A.M., Easton, D.F., Ebeling, T., Edwards, T.L., Ellinor, P.T., Elliott, P., Evangelou, E., Farmaki, A.E., Faul, J.D., Galesloot, T.E., Kiemeney, L.A., Kluivers, K.B., Vermeulen, S.H., Corominas-Galbany, J., Hoyng, C.B., and et al.
Abstract: Contains fulltext : 169801.pdf (publisher's version ) (Closed access), Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
Published: 2017

7. Rare and low-frequency coding variants alter human adult height

Author: Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), Lettre, G. (Guillaume), Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. 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Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of I
Published: 2017
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8. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

Author: Hoggart, C, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, J, Teumer, A, Winkler, T, Tšernikova, N, Luan, J, Mihailov, E, Ehret, G, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, D, Hayward, C, Lopez, M, Franke, L, Russo, A, Heid, I, Salvi, E, Vendantam, S, Arking, D, Boerwinkle, E, Chambers, J, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, J, Porteous, D, Berg, J, Blackwood, D, Campbell, H, Cavanagh, J, Connell, J, Connor, M, Cunningham Burley, S, Deary, I, Dominiczak, A, Ellis, P, Fitzpatrick, B, Ford, I, Gertz, R, Grau, A, Haddow, G, Jackson, C, Kerr, S, Lindsay, R, Mcgilchrist, M, Mcintyre, D, Morris, A, Morton, R, Muir, W, Murray, G, Palmer, C, Pell, J, Philp, A, Porteous, M, Procter, R, Ralston, S, Reid, D, Sinnott, R, Smith, B, St Clair, D, Sullivan, F, Sweetland, M, Ure, J, Watt, G, Wolf, R, Wright, A, de Bakker, P, Bültmann, U, Geleijnse, M, Harst, P, Koppelman, G, Rosmalen, J, van Rossum, L, Smidt, H, Swertz, M, Stolk, R, Alizadeh, B, de Boer, R, Boezen, H, Bruinenberg, M, van der Harst, P, Hillege, H, van der Klauw, M, Navis, G, Ormel, J, Postma, D, Slaets, J, Snieder, H, Wolffenbuttel, B, Wijmenga, C, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Randall, J, Vedantam, S, Willer, C, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Jarick, I, Johansson, A, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Trip, M, Tyrer, J, Van Vliet 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Ferrario, M, Ferrières, J, Frau, F, Gejman, P, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Heard Costa, N, Heath, A, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimaki, M, Koenig, W, Kraja, A, Kumari, M, Karikuulasmaa, N, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Leach, I, Mcknight, B, Medland, S, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palotie, A, Peden, J, Pedersen, N, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stancakova, A, Stark, K, Stephens, J, Stirrups, K, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widen, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wong, A, Zillikens, M, Amouyel, P, Boehm, B, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Hunter, D, Kaplan, R, Karpe, F, Miriammoffatt, N, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, van Duijn, C, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Kemp, J, Lammers, G, Heim, M, Peraita Adrados, R, Schmidt, C, Scott, R, Bell, J, Whitfield, J, Hastie, N, and Da Smith, G
Subjects: Epigenomics, Male, Netherlands Twin Register (NTR), body mass index, gene, SNP, Cancer Research, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Potassium Channels, Glucose Transport Proteins, Facilitative, Medizin, Genome-wide association study, CHILDREN, ddc:616.07, FAMILIES, Body Mass Index, 0302 clinical medicine, Polymorphism (computer science), Genotype, LifeLines Cohort study, GENETICS & HEREDITY, Tandem Pore Domain, Genetics (clinical), ASSOCIATIONS, ddc:616, Genetics, 0303 health sciences, QUANTITATIVE TRAIT LOCI, Ecology, Genomics, Single Nucleotide, Generation Scotland Consortium, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], OBESITY, Physical Sciences, KCNK9 protein, Epigenetics, Female, ALCOHOLISM, Glucose Transport Proteins, Life Sciences & Biomedicine, Statistics (Mathematics), Human, Research Article, VARIANCES, Adult, PENETRANCE, GENES, lcsh:QH426-470, Evolution, European Continental Ancestry Group, Single-nucleotide polymorphism, Biostatistics, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Genomic Imprinting, Potassium Channels, Tandem Pore Domain, Genetic, Behavior and Systematics, SDG 3 - Good Health and Well-being, Genetic linkage, GIANT Consortium, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Statistical Methods, Allele, Polymorphism, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Gene Expression Regulation, Genome-Wide Association Study, Obesity, 030304 developmental biology, 0604 Genetics, Science & Technology, LINKAGE ANALYSIS, SLC2A10 protein, Biology and Life Sciences, Computational Biology, Facilitative, Genome Analysis, Ecology, Evolution, Behavior and Systematic, lcsh:Genetics, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], 3111 Biomedicine, Genomic imprinting, Mathematics, 030217 neurology & neurosurgery, Developmental Biology
Abstract: The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P, Author Summary Large genetic association studies have revealed many genetic factors influencing common traits, such as body mass index (BMI). These studies assume that the effect of genetic variants is the same regardless of whether they are inherited from the mother or the father. In our study, we have developed a new approach that allows us to investigate variants whose impact depends on their parental origin (parent-of-origin effects), in unrelated samples when the parental origin cannot be inferred. This is feasible because at genetic markers at which such effects occur there is increased variability of the trait among individuals who inherited different genetic codes from their mother and their father compared to individuals who inherited the same genetic code from both parents. We applied this methodology to discover genetic markers with parent-of-origin effects (POEs) on BMI. This resulted in six candidate markers showing strong POE association. We then attempted to replicate the POE effects of these markers in family studies (where one can infer the parental origin of the inherited variants). Two of our candidates showed significant association in the family studies, the paternal and maternal effects of these markers were in the opposite direction.
Published: 2014

9. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index

Author: Hoggart, C.J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J.H., Teumer, A., Winkler, T.W., Tsernikova, N., Luan, J., Mihailov, E., Ehret, G.B., Zhang, W., Lamparter, D., Esko, T., Mace, A., Rueger, S., Bochud, P.Y., Barcella, M., Dauvilliers, Y., Benyamin, B., Evans, D.M., Hayward, C., Lopez, M.F., Franke, L., Russo, A., Heid, I.M., Salvi, E., Vendantam, S., Arking, D.E., Boerwinkle, E., Chambers, J.C., Fiorito, G., Grallert, H., Guarrera, S., Homuth, G., Huffman, J.E., Porteous, D., Moradpour, D., Iranzo, A., Hebebrand, J., Kemp, J.P., Lammers, G.J., Aubert, V., Heim, M.H., Martin, N.G., Montgomery, G.W., Peraita-Adrados, R., Santamaria, J., Negro, F., Schmidt, C.O., Scott, R.A., Spector, T.D., Strauch, K., Volzke, H., Wareham, N.J., Yuan, W., Bell, J.T., Chakravarti, A., Kooner, J.S., Peters, A., Matullo, G., Wallaschofski, H., Whitfield, J.B., Paccaud, F., Vollenweider, P., Bergmann, S., Beckmann, J.S., Tafti, M., Hastie, N.D., Cusi, D., Bochud, M., Frayling, T.M., Metspalu, A., Jarvelin, M.R., Scherag, A., Smith, G.D., Borecki, I.B., Rousson, V., Hirschhorn, J.N., Rivolta, C., Loos, R.J., Kutalik, Z., Vermeulen, S., Kiemeney, L.A., et al., Hoggart, C.J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J.H., Teumer, A., Winkler, T.W., Tsernikova, N., Luan, J., Mihailov, E., Ehret, G.B., Zhang, W., Lamparter, D., Esko, T., Mace, A., Rueger, S., Bochud, P.Y., Barcella, M., Dauvilliers, Y., Benyamin, B., Evans, D.M., Hayward, C., Lopez, M.F., Franke, L., Russo, A., Heid, I.M., Salvi, E., Vendantam, S., Arking, D.E., Boerwinkle, E., Chambers, J.C., Fiorito, G., Grallert, H., Guarrera, S., Homuth, G., Huffman, J.E., Porteous, D., Moradpour, D., Iranzo, A., Hebebrand, J., Kemp, J.P., Lammers, G.J., Aubert, V., Heim, M.H., Martin, N.G., Montgomery, G.W., Peraita-Adrados, R., Santamaria, J., Negro, F., Schmidt, C.O., Scott, R.A., Spector, T.D., Strauch, K., Volzke, H., Wareham, N.J., Yuan, W., Bell, J.T., Chakravarti, A., Kooner, J.S., Peters, A., Matullo, G., Wallaschofski, H., Whitfield, J.B., Paccaud, F., Vollenweider, P., Bergmann, S., Beckmann, J.S., Tafti, M., Hastie, N.D., Cusi, D., Bochud, M., Frayling, T.M., Metspalu, A., Jarvelin, M.R., Scherag, A., Smith, G.D., Borecki, I.B., Rousson, V., Hirschhorn, J.N., Rivolta, C., Loos, R.J., Kutalik, Z., Vermeulen, S., Kiemeney, L.A., and et al.
Abstract: Contains fulltext : 136406.pdf (publisher's version ) (Open Access), The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of approximately 4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.
Published: 2014

10. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.

Author: Generation Scotland Consortium, LifeLines Cohort study, GIANT Consortium, Hoggart, C.J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J.H., Teumer, A., Winkler, T.W., Ternikova, N., Luan, J., Mihailov, E., Ehret, G.B., Zhang, W., Lamparter, D., Esko, T., Macé, A., Rüeger, S., Bochud, P.Y., Barcella, M., Dauvilliers, Y., Benyamin, B., Evans, D.M., Hayward, C., Lopez, M.F., Franke, L., Russo, A., Heid, I.M., Salvi, E., Vendantam, S., Arking, D.E., Boerwinkle, E., Chambers, J.C., Fiorito, G., Grallert, H., Guarrera, S., Homuth, G., Huffman, J.E., Porteous, D., Moradpour, D., Iranzo, A., Hebebrand, J., Kemp, J.P., Lammers, G.J., Aubert, V., Heim, M.H., Martin, N.G., Montgomery, G.W., Peraita-Adrados, R., Santamaria, J., Negro, F., Schmidt, C.O., Scott, R.A., Spector, T.D., Strauch, K., Völzke, H., Wareham, N.J., Yuan, W., Bell, J.T., Chakravarti, A., Kooner, J.S., Peters, A., Matullo, G., Wallaschofski, H., Whitfield, J.B., Paccaud, F., Vollenweider, P., Bergmann, S., Beckmann, J.S., Tafti, M., Hastie, N.D., Cusi, D., Bochud, M., Frayling, T.M., Metspalu, A., Jarvelin, M.R., Scherag, A., Smith, G.D., Borecki, I.B., Rousson, V., Hirschhorn, J.N., Rivolta, C., Loos, R.J., Kutalik, Z., Generation Scotland Consortium, LifeLines Cohort study, GIANT Consortium, Hoggart, C.J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J.H., Teumer, A., Winkler, T.W., Ternikova, N., Luan, J., Mihailov, E., Ehret, G.B., Zhang, W., Lamparter, D., Esko, T., Macé, A., Rüeger, S., Bochud, P.Y., Barcella, M., Dauvilliers, Y., Benyamin, B., Evans, D.M., Hayward, C., Lopez, M.F., Franke, L., Russo, A., Heid, I.M., Salvi, E., Vendantam, S., Arking, D.E., Boerwinkle, E., Chambers, J.C., Fiorito, G., Grallert, H., Guarrera, S., Homuth, G., Huffman, J.E., Porteous, D., Moradpour, D., Iranzo, A., Hebebrand, J., Kemp, J.P., Lammers, G.J., Aubert, V., Heim, M.H., Martin, N.G., Montgomery, G.W., Peraita-Adrados, R., Santamaria, J., Negro, F., Schmidt, C.O., Scott, R.A., Spector, T.D., Strauch, K., Völzke, H., Wareham, N.J., Yuan, W., Bell, J.T., Chakravarti, A., Kooner, J.S., Peters, A., Matullo, G., Wallaschofski, H., Whitfield, J.B., Paccaud, F., Vollenweider, P., Bergmann, S., Beckmann, J.S., Tafti, M., Hastie, N.D., Cusi, D., Bochud, M., Frayling, T.M., Metspalu, A., Jarvelin, M.R., Scherag, A., Smith, G.D., Borecki, I.B., Rousson, V., Hirschhorn, J.N., Rivolta, C., Loos, R.J., and Kutalik, Z.
Abstract: The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.
Published: 2014

11. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

Author: Visscher, PM, Hoggart, CJ, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, JH, Teumer, A, Winkler, TW, Tšernikova, N, Luan, J, Mihailov, E, Ehret, GB, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P-Y, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, DM, Hayward, C, Lopez, MF, Franke, L, Russo, A, Heid, IM, Salvi, E, Vendantam, S, Arking, DE, Boerwinkle, E, Chambers, JC, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, JE, Porteous, D, Generation Scotland Consortium, LifeLines Cohort study, GIANT Consortium, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, JP, Lammers, GJ, Aubert, V, Heim, MH, Martin, NG, Montgomery, GW, Peraita-Adrados, R, Santamaria, J, Negro, F, Schmidt, CO, Scott, RA, Spector, TD, Strauch, K, Völzke, H, Wareham, NJ, Yuan, W, Bell, JT, Chakravarti, A, Kooner, JS, Peters, A, Matullo, G, Wallaschofski, H, Whitfield, JB, Paccaud, F, Vollenweider, P, Bergmann, S, Beckmann, JS, Tafti, M, Hastie, ND, Cusi, D, Bochud, M, Frayling, TM, Metspalu, A, Jarvelin, M-R, Scherag, A, Smith, GD, Borecki, IB, Rousson, V, Hirschhorn, JN, Rivolta, C, Loos, RJF, Kutalik, Z, Visscher, PM, Hoggart, CJ, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, JH, Teumer, A, Winkler, TW, Tšernikova, N, Luan, J, Mihailov, E, Ehret, GB, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P-Y, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, DM, Hayward, C, Lopez, MF, Franke, L, Russo, A, Heid, IM, Salvi, E, Vendantam, S, Arking, DE, Boerwinkle, E, Chambers, JC, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, JE, Porteous, D, Generation Scotland Consortium, LifeLines Cohort study, GIANT Consortium, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, JP, Lammers, GJ, Aubert, V, Heim, MH, Martin, NG, Montgomery, GW, Peraita-Adrados, R, Santamaria, J, Negro, F, Schmidt, CO, Scott, RA, Spector, TD, Strauch, K, Völzke, H, Wareham, NJ, Yuan, W, Bell, JT, Chakravarti, A, Kooner, JS, Peters, A, Matullo, G, Wallaschofski, H, Whitfield, JB, Paccaud, F, Vollenweider, P, Bergmann, S, Beckmann, JS, Tafti, M, Hastie, ND, Cusi, D, Bochud, M, Frayling, TM, Metspalu, A, Jarvelin, M-R, Scherag, A, Smith, GD, Borecki, IB, Rousson, V, Hirschhorn, JN, Rivolta, C, Loos, RJF, and Kutalik, Z
Abstract: The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.
Published: 2014

12. Local regulatory networks across two tissues and applications to analyze rare non-coding variants

Author: Reymond, A., Delaneau, O., Zazhytska, M., Popadin, K., Kumar, S., Ambrosini, G., Gschwind, A., Borel, C., Marbach, D., Lamparter, D., Wiederkehr, M., Bergmann, S., Bucher, P., Antonarakis, S. E., and Dermitzakis, E. T.

13. Assessment of network module identification across complex diseases

Author: Choobdar, Sarvenaz, Ahsen, Mehmet E., Natoli, Ted, Lysenko, Artem, Ma, Tianle, Mall, Raghvendra, Marbach, Daniel, Mattia, Tomasoni, Medvedovic, Mario, Menche, Jörg, Mercer, Johnathan, Micarelli, Elisa, Monaco, Alfonso, Narayan, Rajiv, Müller, Felix, Narykov, Oleksandr, Norman, Thea, Park, Sungjoon, Perfetto, Livia, Perrin, Dimitri, Pirrò, Stefano, Przytycka, Teresa M., DREAM Module Identification Challenge Consortium, Qian, Xiaoning, Raman, Karthik, Ramazzotti, Daniele, Ramsahai, Emilie, Ravindran, Balaraman, Rennert, Philip, Sáez Rodríguez, Julio, Schärfe, Charlotta, Sharan, Roded, Shi, Ning, Subramanian, Aravind, Shin, Wonho, Shu, Hai, Sinha, Himanshu, Slonim, Donna K., Spinelli, Lionel, Srinivasan, Suhas, Suver, Christine, Szklarczyk, Damian, Tangaro, Sabina, Zhang, Jitao D., Thiagarajan, Suresh, Tichit, Laurent, Tiede, Thorsten, Tripathi, Beethika, Tsherniak, Aviad, Tsunoda, Tatsuhiko, Türei, Dénes, Ullah, Ehsan, Vahedi, Golnaz, Valdeolivas, Alberto, Stolovitzky, Gustavo, Vivek, Jayaswal, von Mering, Christian, Waagmeester, Andra, Wang, Bo, Wang, Yijie, Weir, Barbara A., White, Shana, Winkler, Sebastian, Xu, Ke, Xu, Taosheng, Kutalik, Zoltán, Yan, Chunhua, Yang, Liuqing, Yu, Kaixian, Yu, Xiangtian, Zaffaroni, Gaia, Zaslavskiy, Mikhail, Zeng, Tao, Zhang, Lu, Zhang, Weijia, Lage, Kasper, Zhang, Lixia, Zhang, Xinyu, Zhang, Junpeng, Zhou, Xin, Zhou, Jiarui, Zhu, Hongtu, Zhu, Junjie, Zuccon, Guido, Crawford, Jake, Cowen, Lenore J., Bergmann, Sven, Aicheler, Fabian, Amoroso, Nicola, Arenas, Alex, Azhagesan, Karthik, Baker, Aaron, Banf, Michael, Batzoglou, Serafim, Tomasoni, Mattia, Baudot, Anaïs, Bellotti, Roberto, Boroevich, Keith A., Brun, Christine, Cai, Stanley, Caldera, Michael, Calderone, Alberto, Cesareni, Gianni, Chen, Weiqi, Fang, Tao, Chichester, Christine, Cowen, Lenore, Cui, Hongzhu, Dao, Phuong, De Domenico, Manlio, Dhroso, Andi, Didier, Gilles, Divine, Mathew, Lamparter, David, Del Sol, Antonio, Feng, Xuyang, Flores-Canales, Jose C., Fortunato, Santo, Gitter, Anthony, Gorska, Anna, Guan, Yuanfang, Guénoche, Alain, Gómez, Sergio, Lin, Junyuan, Hamza, Hatem, Hartmann, András, He, Shan, Heijs, Anton, Heinrich, Julian, Hescott, Benjamin, Hu, Xiaozhe, Hu, Ying, Huang, Xiaoqing, Hughitt, V. Keith, Jeon, Minji, Jeub, Lucas, Johnson, Nathan T., Joo, Keehyoung, Joung, InSuk, Jung, Sascha, Kalko, Susana G., Kamola, Piotr J., Kang, Jaewoo, Kaveelerdpotjana, Benjapun, Kim, Minjun, Kim, Yoo-Ah, Kohlbacher, Oliver, Korkin, Dmitry, Krzysztof, Kiryluk, Kunji, Khalid, Kutalik, Zoltàn, Lang-Brown, Sean, Le, Thuc Duy, Lee, Jooyoung, Lee, Sunwon, Lee, Juyong, Li, Dong, Li, Jiuyong, Liu, Lin, Loizou, Antonis, Luo, Zhenhua, Choobdar, Sarvenaz, Ahsen, Mehmet E., Crawford, Jake, Tomasoni, Mattia, Le, Thuc Duy, Li, Jiuyong, Liu, Lin, Zhang, W, Marbach, D, The DREAM Module Identification Challenge Consortium, Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Spinelli, Lionel, Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Theories and Approaches of Genomic Complexity (TAGC), DREAM Module Identification Challenge Consortium, Aicheler, F., Amoroso, N., Arenas, A., Azhagesan, K., Baker, A., Banf, M., Batzoglou, S., Baudot, A., Bellotti, R., Bergmann, S., Boroevich, K.A., Brun, C., Cai, S., Caldera, M., Calderone, A., Cesareni, G., Chen, W., Chichester, C., Choobdar, S., Cowen, L., Crawford, J., Cui, H., Dao, P., De Domenico, M., Dhroso, A., Didier, G., Divine, M., Del Sol, A., Fang, T., Feng, X., Flores-Canales, J.C., Fortunato, S., Gitter, A., Gorska, A., Guan, Y., Guénoche, A., Gómez, S., Hamza, H., Hartmann, A., He, S., Heijs, A., Heinrich, J., Hescott, B., Hu, X., Hu, Y., Huang, X., Hughitt, V.K., Jeon, M., Jeub, L., Johnson, N.T., Joo, K., Joung, I., Jung, S., Kalko, S.G., Kamola, P.J., Kang, J., Kaveelerdpotjana, B., Kim, M., Kim, Y.A., Kohlbacher, O., Korkin, D., Krzysztof, K., Kunji, K., Kutalik, Z., Lage, K., Lamparter, D., Lang-Brown, S., Le, T.D., Lee, J., Lee, S., Li, D., Li, J., Lin, J., Liu, L., Loizou, A., Luo, Z., Lysenko, A., Ma, T., Mall, R., Marbach, D., Mattia, T., Medvedovic, M., Menche, J., Mercer, J., Micarelli, E., Monaco, A., Müller, F., Narayan, R., Narykov, O., Natoli, T., Norman, T., Park, S., Perfetto, L., Perrin, D., Pirrò, S., Przytycka, T.M., Qian, X., Raman, K., Ramazzotti, D., Ramsahai, E., Ravindran, B., Rennert, P., Saez-Rodriguez, J., Schärfe, C., Sharan, R., Shi, N., Shin, W., Shu, H., Sinha, H., Slonim, D.K., Spinelli, L., Srinivasan, S., Subramanian, A., Suver, C., Szklarczyk, D., Tangaro, S., Thiagarajan, S., Tichit, L., Tiede, T., Tripathi, B., Tsherniak, A., Tsunoda, T., Türei, D., Ullah, E., Vahedi, G., Valdeolivas, A., Vivek, J., von Mering, C., Waagmeester, A., Wang, B., Wang, Y., Weir, B.A., White, S., Winkler, S., Xu, K., Xu, T., Yan, C., Yang, L., Yu, K., Yu, X., Zaffaroni, G., Zaslavskiy, M., Zeng, T., Zhang, J.D., Zhang, L., Zhang, W., Zhang, X., Zhang, J., Zhou, X., Zhou, J., Zhu, H., Zhu, J., and Zuccon, G.
Subjects: Identification methods, Cellular signalling networks, Computer science, Population genetics, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Gene regulatory network, DREAM challenge, network, modules, predictions, Genome-wide association study, Computational biology, Biochemistry, Models, Biological, Polymorphism, Single Nucleotide, Gene regulatory networks, Functional clustering, 03 medical and health sciences, Human disease, Humans, Disease, ddc:610, Protein Interaction Maps, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Network module, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Network topology, Gene Expression Profiling, Computational Biology, Cell Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Gene expression profiling, [SDV] Life Sciences [q-bio], Molecular network, Phenotype, Protein network, Network Module Identification, Analysis, Algorithms, Biotechnology, Genome-Wide Association Study
Abstract: Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the ‘Disease Module Identification DREAM Challenge’, an open competition to comprehensively assess module identification methods across diverse protein–protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology., In this DREAM challenge, 75 methods for the identification of disease-relevant modules from molecular networks are compared and validated with GWAS data. The authors provide practical guidelines for users and establish benchmarks for network analysis.
Published: 2019

14. Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.

Author: Emmenegger M, De Cecco E, Lamparter D, Jacquat RPB, Riou J, Menges D, Ballouz T, Ebner D, Schneider MM, Morales IC, Doğançay B, Guo J, Wiedmer A, Domange J, Imeri M, Moos R, Zografou C, Batkitar L, Madrigal L, Schneider D, Trevisan C, Gonzalez-Guerra A, Carrella A, Dubach IL, Xu CK, Meisl G, Kosmoliaptsis V, Malinauskas T, Burgess-Brown N, Owens R, Hatch S, Mongkolsapaya J, Screaton GR, Schubert K, Huck JD, Liu F, Pojer F, Lau K, Hacker D, Probst-Müller E, Cervia C, Nilsson J, Boyman O, Saleh L, Spanaus K, von Eckardstein A, Schaer DJ, Ban N, Tsai CJ, Marino J, Schertler GFX, Ebert N, Thiel V, Gottschalk J, Frey BM, Reimann RR, Hornemann S, Ring AM, Knowles TPJ, Puhan MA, Althaus CL, Xenarios I, Stuart DI, and Aguzzi A
Abstract: Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae., Competing Interests: TPJK is a member of the board of directors of Fluidic Analytics. AA is a member of the board of directors of Mabylon AG which has funded antibody-related work in the Aguzzi lab in the past. All other authors declare no competing interests., (© 2023 The Authors.)
Published: 2023
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15. Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency.

Author: Forny P, Bonilla X, Lamparter D, Shao W, Plessl T, Frei C, Bingisser A, Goetze S, van Drogen A, Harshman K, Pedrioli PGA, Howald C, Poms M, Traversi F, Bürer C, Cherkaoui S, Morscher RJ, Simmons L, Forny M, Xenarios I, Aebersold R, Zamboni N, Rätsch G, Dermitzakis ET, Wollscheid B, Baumgartner MR, and Froese DS
Subjects: Mice, Animals, Glutamine, Multiomics, Methylmalonyl-CoA Mutase genetics, Methylmalonyl-CoA Mutase metabolism, Metabolism, Inborn Errors genetics
Abstract: Methylmalonic aciduria (MMA) is an inborn error of metabolism with multiple monogenic causes and a poorly understood pathogenesis, leading to the absence of effective causal treatments. Here we employ multi-layered omics profiling combined with biochemical and clinical features of individuals with MMA to reveal a molecular diagnosis for 177 out of 210 (84%) cases, the majority (148) of whom display pathogenic variants in methylmalonyl-CoA mutase (MMUT). Stratification of these data layers by disease severity shows dysregulation of the tricarboxylic acid cycle and its replenishment (anaplerosis) by glutamine. The relevance of these disturbances is evidenced by multi-organ metabolomics of a hemizygous Mmut mouse model as well as through identification of physical interactions between MMUT and glutamine anaplerotic enzymes. Using stable-isotope tracing, we find that treatment with dimethyl-oxoglutarate restores deficient tricarboxylic acid cycling. Our work highlights glutamine anaplerosis as a potential therapeutic intervention point in MMA., (© 2023. The Author(s).)
Published: 2023
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16. A framework for integrating directed and undirected annotations to build explanatory models of cis-eQTL data.

Author: Lamparter D, Bhatnagar R, Hebestreit K, Belgard TG, Zhang A, and Hanson-Smith V
Subjects: Algorithms, Bayes Theorem, Chromosome Mapping, DNA analysis, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Genome, Human, Genomics, Genotype, Humans, Molecular Sequence Annotation, Monocytes metabolism, Software, Computational Biology methods, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract: A longstanding goal of regulatory genetics is to understand how variants in genome sequences lead to changes in gene expression. Here we present a method named Bayesian Annotation Guided eQTL Analysis (BAGEA), a variational Bayes framework to model cis-eQTLs using directed and undirected genomic annotations. We used BAGEA to integrate directed genomic annotations with eQTL summary statistics from tissues of various origins. This analysis revealed epigenetic marks that are relevant for gene expression in different tissues and cell types. We estimated the predictive power of the models that were fitted based on directed genomic annotations. This analysis showed that, depending on the underlying eQTL data used, the directed genomic annotations could predict up to 1.5% of the variance observed in the expression of genes with top nominal eQTL association p-values < 10-7. For genes with estimated effect sizes in the top 25% quantile, up to 5% of the expression variance could be predicted. Based on our results, we recommend the use of BAGEA for the analysis of cis-eQTL data to reveal annotations relevant to expression biology., Competing Interests: The authors of this paper are current and former employees of Verge Genomics, a venture-backed startup company. The authors have declared that no competing interests exist. This does not alter our adherence to all PLOS Computational Biology policies on sharing data and materials.
Published: 2020
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17. Assessment of network module identification across complex diseases.

Author: Choobdar S, Ahsen ME, Crawford J, Tomasoni M, Fang T, Lamparter D, Lin J, Hescott B, Hu X, Mercer J, Natoli T, Narayan R, Subramanian A, Zhang JD, Stolovitzky G, Kutalik Z, Lage K, Slonim DK, Saez-Rodriguez J, Cowen LJ, Bergmann S, and Marbach D
Subjects: Algorithms, Gene Expression Profiling, Humans, Phenotype, Protein Interaction Maps, Computational Biology methods, Disease genetics, Gene Regulatory Networks, Genome-Wide Association Study, Models, Biological, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract: Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the 'Disease Module Identification DREAM Challenge', an open competition to comprehensively assess module identification methods across diverse protein-protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.
Published: 2019
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18. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Author: Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Blüher M, Boehnke M, Boeing H, Boerwinkle E, Böger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Galbany JC, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Di Angelantonio E, Drenos F, Du M, Dubé MP, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki AE, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe HJ, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland Ø, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson JH, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jørgensen ME, Jørgensen T, Jukema JW, Kahali B, Kahn RS, Kähönen M, Kamstrup PR, Kanoni S, Kaprio J, Karaleftheri M, Kardia SLR, Karpe F, Kathiresan S, Kee F, Kiemeney LA, Kim E, Kitajima H, Komulainen P, Kooner JS, Kooperberg C, Korhonen T, Kovacs P, Kuivaniemi H, Kutalik Z, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange EM, Lange LA, Langenberg C, Larson EB, Lee NR, Lehtimäki T, Lewis CE, Li H, Li J, Li-Gao R, Lin H, Lin KH, Lin LA, Lin X, Lind L, Lindström J, Linneberg A, Liu CT, Liu DJ, Liu Y, Lo KS, Lophatananon A, Lotery AJ, Loukola A, Luan J, Lubitz SA, Lyytikäinen LP, Männistö S, Marenne G, Mazul AL, McCarthy MI, McKean-Cowdin R, Medland SE, Meidtner K, Milani L, Mistry V, Mitchell P, Mohlke KL, Moilanen L, Moitry M, Montgomery GW, Mook-Kanamori DO, Moore C, Mori TA, Morris AD, Morris AP, Müller-Nurasyid M, Munroe PB, Nalls MA, Narisu N, Nelson CP, Neville M, Nielsen SF, Nikus K, Njølstad PR, Nordestgaard BG, Nyholt DR, O'Connel JR, O'Donoghue ML, Loohuis LMO, Ophoff RA, Owen KR, Packard CJ, Padmanabhan S, Palmer CNA, Palmer ND, Pasterkamp G, Patel AP, Pattie A, Pedersen O, Peissig PL, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Pers TH, Person TN, Peters A, Petersen ERB, Peyser PA, Pirie A, Polasek O, Polderman TJ, Puolijoki H, Raitakari OT, Rasheed A, Rauramaa R, Reilly DF, Renström F, Rheinberger M, Ridker PM, Rioux JD, Rivas MA, Roberts DJ, Robertson NR, Robino A, Rolandsson O, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Sapkota Y, Sattar N, Schoen RE, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe MP, Shah SH, Sheu WH, Sim X, Slater AJ, Small KS, Smith AV, Southam L, Spector TD, Speliotes EK, Starr JM, Stefansson K, Steinthorsdottir V, Stirrups KE, Strauch K, Stringham HM, Stumvoll M, Sun L, Surendran P, Swift AJ, Tada H, Tansey KE, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorleifsson G, Thorsteinsdottir U, Thuesen BH, Tönjes A, Tromp G, Trompet S, Tsafantakis E, Tuomilehto J, Tybjaerg-Hansen A, Tyrer JP, Uher R, Uitterlinden AG, Uusitupa M, Laan SW, Duijn CM, Leeuwen N, van Setten J, Vanhala M, Varbo A, Varga TV, Varma R, Edwards DRV, Vermeulen SH, Veronesi G, Vestergaard H, Vitart V, Vogt TF, Völker U, Vuckovic D, Wagenknecht LE, Walker M, Wallentin L, Wang F, Wang CA, Wang S, Wang Y, Ware EB, Wareham NJ, Warren HR, Waterworth DM, Wessel J, White HD, Willer CJ, Wilson JG, Witte DR, Wood AR, Wu Y, Yaghootkar H, Yao J, Yao P, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zhao W, Zhou W, Zondervan KT, Rotter JI, Pospisilik JA, Rivadeneira F, Borecki IB, Deloukas P, Frayling TM, Lettre G, North KE, Lindgren CM, Hirschhorn JN, and Loos RJF
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
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19. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Author: Justice AE, Karaderi T, Highland HM, Young KL, Graff M, Lu Y, Turcot V, Auer PL, Fine RS, Guo X, Schurmann C, Lempradl A, Marouli E, Mahajan A, Winkler TW, Locke AE, Medina-Gomez C, Esko T, Vedantam S, Giri A, Lo KS, Alfred T, Mudgal P, Ng MCY, Heard-Costa NL, Feitosa MF, Manning AK, Willems SM, Sivapalaratnam S, Abecasis G, Alam DS, Allison M, Amouyel P, Arzumanyan Z, Balkau B, Bastarache L, Bergmann S, Bielak LF, Blüher M, Boehnke M, Boeing H, Boerwinkle E, Böger CA, Bork-Jensen J, Bottinger EP, Bowden DW, Brandslund I, Broer L, Burt AA, Butterworth AS, Caulfield MJ, Cesana G, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Collins FS, Cook JP, Cox AJ, Crosslin DS, Danesh J, de Bakker PIW, Denus S, Mutsert R, Dedoussis G, Demerath EW, Dennis JG, Denny JC, Di Angelantonio E, Dörr M, Drenos F, Dubé MP, Dunning AM, Easton DF, Elliott P, Evangelou E, Farmaki AE, Feng S, Ferrannini E, Ferrieres J, Florez JC, Fornage M, Fox CS, Franks PW, Friedrich N, Gan W, Gandin I, Gasparini P, Giedraitis V, Girotto G, Gorski M, Grallert H, Grarup N, Grove ML, Gustafsson S, Haessler J, Hansen T, Hattersley AT, Hayward C, Heid IM, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Hung YJ, Hveem K, Ikram MA, Ingelsson E, Jackson AU, Jarvik GP, Jia Y, Jørgensen T, Jousilahti P, Justesen JM, Kahali B, Karaleftheri M, Kardia SLR, Karpe F, Kee F, Kitajima H, Komulainen P, Kooner JS, Kovacs P, Krämer BK, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange LA, Langenberg C, Larson EB, Lee NR, Lee WJ, Lehtimäki T, Lewis CE, Li H, Li J, Li-Gao R, Lin LA, Lin X, Lind L, Lindström J, Linneberg A, Liu CT, Liu DJ, Luan J, Lyytikäinen LP, MacGregor S, Mägi R, Männistö S, Marenne G, Marten J, Masca NGD, McCarthy MI, Meidtner K, Mihailov E, Moilanen L, Moitry M, Mook-Kanamori DO, Morgan A, Morris AP, Müller-Nurasyid M, Munroe PB, Narisu N, Nelson CP, Neville M, Ntalla I, O'Connell JR, Owen KR, Pedersen O, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Pers TH, Ewing A, Polasek O, Raitakari OT, Rasheed A, Raulerson CK, Rauramaa R, Reilly DF, Reiner AP, Ridker PM, Rivas MA, Robertson NR, Robino A, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe M, Sim X, Slater AJ, Small KS, Smith BH, Smith JA, Southam L, Spector TD, Speliotes EK, Stefansson K, Steinthorsdottir V, Stirrups KE, Strauch K, Stringham HM, Stumvoll M, Sun L, Surendran P, Swart KMA, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorleifsson G, Thorsteinsdottir U, Thuesen BH, Tönjes A, Torres M, Tsafantakis E, Tuomilehto J, Uitterlinden AG, Uusitupa M, van Duijn CM, Vanhala M, Varma R, Vermeulen SH, Vestergaard H, Vitart V, Vogt TF, Vuckovic D, Wagenknecht LE, Walker M, Wallentin L, Wang F, Wang CA, Wang S, Wareham NJ, Warren HR, Waterworth DM, Wessel J, White HD, Willer CJ, Wilson JG, Wood AR, Wu Y, Yaghootkar H, Yao J, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zheng H, Zhou W, Zillikens MC, Rivadeneira F, Borecki IB, Pospisilik JA, Deloukas P, Frayling TM, Lettre G, Mohlke KL, Rotter JI, Kutalik Z, Hirschhorn JN, Cupples LA, Loos RJF, North KE, and Lindgren CM
Subjects: Animals, Body Fat Distribution methods, Body Mass Index, Case-Control Studies, Drosophila genetics, Exome genetics, Female, Gene Frequency genetics, Genome-Wide Association Study methods, Humans, Male, Risk Factors, Waist-Hip Ratio methods, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Homeostasis genetics, Lipids genetics, Proteins genetics
Abstract: Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
Published: 2019
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20. Improved small scale production of iodine-124 for radiolabeling and clinical applications.

Author: Lamparter D, Hallmann B, Hänscheid H, Boschi F, Malinconico M, and Samnick S
Subjects: Cyclotrons, Equipment Design, Humans, Iodine Radioisotopes standards, Positron-Emission Tomography, Quality Control, Radiochemistry instrumentation, Radiochemistry standards, Radiopharmaceuticals standards, Sodium Iodide isolation & purification, Sodium Iodide standards, Iodine Radioisotopes isolation & purification, Radiochemistry methods, Radiopharmaceuticals isolation & purification
Abstract: Aim: This work describes a small-scale production of iodine-124 using a 16.5 MeV cyclotron, and a subsequent validation of the formulated sodium [124I]iodide solution for routinely clinical applications., Methods: Iodine-124 ( 124 I) was produced via the 124 Te(p, n) 124 I reaction using a 16.5 MeV GE PETtrace® cyclotron. Irradiation was performed with a pre-prepared solid target consisting of [ 124 Te]TeO 2 (99.93%) and Al 2 O 3 . Different layer thicknesses, irradiation and extraction parameters were tested. After irradiation at the cyclotron, the shuttle with irradiated material was transferred fully automatically via a tube system to the Comecer ALCEO ® Halogen 2.0 extraction unit. Iodine-124 was subsequently extracted in form of sodium [ 124 I]iodide ([ 124 I]NaI) in 0.05 N aqueous NaOH solution, followed by reconstitution and validation for preclinical and clinical uses., Results: Good result was achieved using a beam degradation foil of 500 µm thickness in combination with beam currents between 10 and 15 µA. Under these conditions, up to 150 MBq no-carrier-added [ 124 I]NaI was obtained after a 2 h irradiation time in less than 500 µl 0.05 N NaOH. Isolation of [ 124 I]NaI, including evaporation and extraction at the ALCEO ® Halogen EVP unit was accomplished in 90 min 24 h after production (irradiation), the amount of iodine-123 as assessed by gamma-ray spectroscopy was less than 1.5%. The undesirable iodine-125 was not detectable by gamma spectroscopy. The extracted [ 124 I]NaI could be used directly for radiolabeling purposes, and after buffering with phosphate buffered saline (PBS) and sterile filtration for clinical applications., Conclusions: Through the optimized conditions for irradiation and extraction, iodine-124 was produced in good radiochemical yields and high radionuclide purity. The generated injectable [ 124 I]NaI solution was sterile, non-pyrogenic and ready for preclinical and clinical applications after a sterile filtration through a 0.22 µm membrane filter., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Published: 2018
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21. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Author: Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Blüher M, Boehnke M, Boeing H, Boerwinkle E, Böger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Corominas Galbany J, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Angelantonio E, Drenos F, Du M, Dubé MP, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki AE, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe HJ, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland Ø, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson JH, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jørgensen ME, Jørgensen T, Jukema JW, Kahali B, Kahn RS, Kähönen M, Kamstrup PR, Kanoni S, Kaprio J, Karaleftheri M, Kardia SLR, Karpe F, Kathiresan S, Kee F, Kiemeney LA, Kim E, Kitajima H, Komulainen P, Kooner JS, Kooperberg C, Korhonen T, Kovacs P, Kuivaniemi H, Kutalik Z, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange EM, Lange LA, Langenberg C, Larson EB, Lee NR, Lehtimäki T, Lewis CE, Li H, Li J, Li-Gao R, Lin H, Lin KH, Lin LA, Lin X, Lind L, Lindström J, Linneberg A, Liu CT, Liu DJ, Liu Y, Lo KS, Lophatananon A, Lotery AJ, Loukola A, Luan J, Lubitz SA, Lyytikäinen LP, Männistö S, Marenne G, Mazul AL, McCarthy MI, McKean-Cowdin R, Medland SE, Meidtner K, Milani L, Mistry V, Mitchell P, Mohlke KL, Moilanen L, Moitry M, Montgomery GW, Mook-Kanamori DO, Moore C, Mori TA, Morris AD, Morris AP, Müller-Nurasyid M, Munroe PB, Nalls MA, Narisu N, Nelson CP, Neville M, Nielsen SF, Nikus K, Njølstad PR, Nordestgaard BG, Nyholt DR, O'Connel JR, O'Donoghue ML, Olde Loohuis LM, Ophoff RA, Owen KR, Packard CJ, Padmanabhan S, Palmer CNA, Palmer ND, Pasterkamp G, Patel AP, Pattie A, Pedersen O, Peissig PL, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Pers TH, Person TN, Peters A, Petersen ERB, Peyser PA, Pirie A, Polasek O, Polderman TJ, Puolijoki H, Raitakari OT, Rasheed A, Rauramaa R, Reilly DF, Renström F, Rheinberger M, Ridker PM, Rioux JD, Rivas MA, Roberts DJ, Robertson NR, Robino A, Rolandsson O, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Sapkota Y, Sattar N, Schoen RE, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe MP, Shah SH, Sheu WH, Sim X, Slater AJ, Small KS, Smith AV, Southam L, Spector TD, Speliotes EK, Starr JM, Stefansson K, Steinthorsdottir V, Stirrups KE, Strauch K, Stringham HM, Stumvoll M, Sun L, Surendran P, Swift AJ, Tada H, Tansey KE, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorleifsson G, Thorsteinsdottir U, Thuesen BH, Tönjes A, Tromp G, Trompet S, Tsafantakis E, Tuomilehto J, Tybjaerg-Hansen A, Tyrer JP, Uher R, Uitterlinden AG, Uusitupa M, Laan SW, Duijn CM, Leeuwen N, van Setten J, Vanhala M, Varbo A, Varga TV, Varma R, Velez Edwards DR, Vermeulen SH, Veronesi G, Vestergaard H, Vitart V, Vogt TF, Völker U, Vuckovic D, Wagenknecht LE, Walker M, Wallentin L, Wang F, Wang CA, Wang S, Wang Y, Ware EB, Wareham NJ, Warren HR, Waterworth DM, Wessel J, White HD, Willer CJ, Wilson JG, Witte DR, Wood AR, Wu Y, Yaghootkar H, Yao J, Yao P, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zhou W, Zondervan KT, Rotter JI, Pospisilik JA, Rivadeneira F, Borecki IB, Deloukas P, Frayling TM, Lettre G, North KE, Lindgren CM, Hirschhorn JN, and Loos RJF
Abstract: In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.
Published: 2018
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22. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

Author: Corre T, Arjona FJ, Hayward C, Youhanna S, de Baaij JHF, Belge H, Nägele N, Debaix H, Blanchard MG, Traglia M, Harris SE, Ulivi S, Rueedi R, Lamparter D, Macé A, Sala C, Lenarduzzi S, Ponte B, Pruijm M, Ackermann D, Ehret G, Baptista D, Polasek O, Rudan I, Hurd TW, Hastie ND, Vitart V, Waeber G, Kutalik Z, Bergmann S, Vargas-Poussou R, Konrad M, Gasparini P, Deary IJ, Starr JM, Toniolo D, Vollenweider P, Hoenderop JGJ, Bindels RJM, Bochud M, and Devuyst O
Subjects: Adiposity genetics, Animals, GTP-Binding Proteins genetics, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Insulin blood, Insulin Resistance genetics, Magnesium administration & dosage, Mice, Obesity genetics, Phenotype, Polymorphism, Single Nucleotide, RNA, Messenger metabolism, Zebrafish, Zebrafish Proteins genetics, ADP-Ribosylation Factors genetics, Homeostasis genetics, Kidney metabolism, Magnesium blood, Magnesium urine, TRPM Cation Channels genetics
Abstract: Magnesium (Mg 2+ ) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg 2+ , which is crucial for Mg 2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg 2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 ( P= 4.4×10 -13 ) near TRPM6 , which encodes an epithelial Mg 2+ channel, and rs35929 ( P= 2.1×10 -11 ), a variant of ARL15 , which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg 2+ regulated the expression of the highly conserved ARL15 ortholog arl15b , and arl15b knockdown resulted in renal Mg 2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg 2+ deficiency to insulin resistance and obesity., (Copyright © 2018 by the American Society of Nephrology.)
Published: 2018
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23. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Author: Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Blüher M, Boehnke M, Boeing H, Boerwinkle E, Böger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Corominas Galbany J, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Di Angelantonio E, Drenos F, Du M, Dubé MP, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki AE, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe HJ, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland Ø, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson JH, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jørgensen ME, Jørgensen T, Jukema JW, Kahali B, Kahn RS, Kähönen M, Kamstrup PR, Kanoni S, Kaprio J, Karaleftheri M, Kardia SLR, Karpe F, Kathiresan S, Kee F, Kiemeney LA, Kim E, Kitajima H, Komulainen P, Kooner JS, Kooperberg C, Korhonen T, Kovacs P, Kuivaniemi H, Kutalik Z, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange EM, Lange LA, Langenberg C, Larson EB, Lee NR, Lehtimäki T, Lewis CE, Li H, Li J, Li-Gao R, Lin H, Lin KH, Lin LA, Lin X, Lind L, Lindström J, Linneberg A, Liu CT, Liu DJ, Liu Y, Lo KS, Lophatananon A, Lotery AJ, Loukola A, Luan J, Lubitz SA, Lyytikäinen LP, Männistö S, Marenne G, Mazul AL, McCarthy MI, McKean-Cowdin R, Medland SE, Meidtner K, Milani L, Mistry V, Mitchell P, Mohlke KL, Moilanen L, Moitry M, Montgomery GW, Mook-Kanamori DO, Moore C, Mori TA, Morris AD, Morris AP, Müller-Nurasyid M, Munroe PB, Nalls MA, Narisu N, Nelson CP, Neville M, Nielsen SF, Nikus K, Njølstad PR, Nordestgaard BG, Nyholt DR, O'Connel JR, O'Donoghue ML, Olde Loohuis LM, Ophoff RA, Owen KR, Packard CJ, Padmanabhan S, Palmer CNA, Palmer ND, Pasterkamp G, Patel AP, Pattie A, Pedersen O, Peissig PL, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Pers TH, Person TN, Peters A, Petersen ERB, Peyser PA, Pirie A, Polasek O, Polderman TJ, Puolijoki H, Raitakari OT, Rasheed A, Rauramaa R, Reilly DF, Renström F, Rheinberger M, Ridker PM, Rioux JD, Rivas MA, Roberts DJ, Robertson NR, Robino A, Rolandsson O, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Sapkota Y, Sattar N, Schoen RE, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe MP, Shah SH, Sheu WH, Sim X, Slater AJ, Small KS, Smith AV, Southam L, Spector TD, Speliotes EK, Starr JM, Stefansson K, Steinthorsdottir V, Stirrups KE, Strauch K, Stringham HM, Stumvoll M, Sun L, Surendran P, Swift AJ, Tada H, Tansey KE, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorleifsson G, Thorsteinsdottir U, Thuesen BH, Tönjes A, Tromp G, Trompet S, Tsafantakis E, Tuomilehto J, Tybjaerg-Hansen A, Tyrer JP, Uher R, Uitterlinden AG, Uusitupa M, Laan SW, Duijn CM, Leeuwen N, van Setten J, Vanhala M, Varbo A, Varga TV, Varma R, Velez Edwards DR, Vermeulen SH, Veronesi G, Vestergaard H, Vitart V, Vogt TF, Völker U, Vuckovic D, Wagenknecht LE, Walker M, Wallentin L, Wang F, Wang CA, Wang S, Wang Y, Ware EB, Wareham NJ, Warren HR, Waterworth DM, Wessel J, White HD, Willer CJ, Wilson JG, Witte DR, Wood AR, Wu Y, Yaghootkar H, Yao J, Yao P, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zhao W, Zhou W, Zondervan KT, Rotter JI, Pospisilik JA, Rivadeneira F, Borecki IB, Deloukas P, Frayling TM, Lettre G, North KE, Lindgren CM, Hirschhorn JN, and Loos RJF
Subjects: Adult, Animals, Drosophila genetics, Female, Gene Frequency, Humans, Male, Proteins genetics, Syndrome, Body Mass Index, Energy Intake genetics, Energy Metabolism genetics, Genetic Variation, Obesity genetics
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Published: 2018
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24. Metabomatching: Using genetic association to identify metabolites in proton NMR spectroscopy.

Author: Rueedi R, Mallol R, Raffler J, Lamparter D, Friedrich N, Vollenweider P, Waeber G, Kastenmüller G, Kutalik Z, and Bergmann S
Subjects: Humans, Databases, Genetic, Genome-Wide Association Study methods, Magnetic Resonance Spectroscopy methods, Metabolomics methods
Abstract: A metabolome-wide genome-wide association study (mGWAS) aims to discover the effects of genetic variants on metabolome phenotypes. Most mGWASes use as phenotypes concentrations of limited sets of metabolites that can be identified and quantified from spectral information. In contrast, in an untargeted mGWAS both identification and quantification are forgone and, instead, all measured metabolome features are tested for association with genetic variants. While the untargeted approach does not discard data that may have eluded identification, the interpretation of associated features remains a challenge. To address this issue, we developed metabomatching to identify the metabolites underlying significant associations observed in untargeted mGWASes on proton NMR metabolome data. Metabomatching capitalizes on genetic spiking, the concept that because metabolome features associated with a genetic variant tend to correspond to the peaks of the NMR spectrum of the underlying metabolite, genetic association can allow for identification. Applied to the untargeted mGWASes in the SHIP and CoLaus cohorts and using 180 reference NMR spectra of the urine metabolome database, metabomatching successfully identified the underlying metabolite in 14 of 19, and 8 of 9 associations, respectively. The accuracy and efficiency of our method make it a strong contender for facilitating or complementing metabolomics analyses in large cohorts, where the availability of genetic, or other data, enables our approach, but targeted quantification is limited.
Published: 2017
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25. Rare and low-frequency coding variants alter human adult height.

Author: Marouli E, Graff M, Medina-Gomez C, Lo KS, Wood AR, Kjaer TR, Fine RS, Lu Y, Schurmann C, Highland HM, Rüeger S, Thorleifsson G, Justice AE, Lamparter D, Stirrups KE, Turcot V, Young KL, Winkler TW, Esko T, Karaderi T, Locke AE, Masca NG, Ng MC, Mudgal P, Rivas MA, Vedantam S, Mahajan A, Guo X, Abecasis G, Aben KK, Adair LS, Alam DS, Albrecht E, Allin KH, Allison M, Amouyel P, Appel EV, Arveiler D, Asselbergs FW, Auer PL, Balkau B, Banas B, Bang LE, Benn M, Bergmann S, Bielak LF, Blüher M, Boeing H, Boerwinkle E, Böger CA, Bonnycastle LL, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Burt AA, Butterworth AS, Carey DJ, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Galbany JC, Cox AJ, Cuellar-Partida G, Danesh J, Davies G, de Bakker PI, de Borst GJ, de Denus S, de Groot MC, de Mutsert R, Deary IJ, Dedoussis G, Demerath EW, den Hollander AI, Dennis JG, Di Angelantonio E, Drenos F, Du M, Dunning AM, Easton DF, Ebeling T, Edwards TL, Ellinor PT, Elliott P, Evangelou E, Farmaki AE, Faul JD, Feitosa MF, Feng S, Ferrannini E, Ferrario MM, Ferrieres J, Florez JC, Ford I, Fornage M, Franks PW, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Giedraitis V, Giri A, Girotto G, Gordon SD, Gordon-Larsen P, Gorski M, Grarup N, Grove ML, Gudnason V, Gustafsson S, Hansen T, Harris KM, Harris TB, Hattersley AT, Hayward C, He L, Heid IM, Heikkilä K, Helgeland Ø, Hernesniemi J, Hewitt AW, Hocking LJ, Hollensted M, Holmen OL, Hovingh GK, Howson JM, Hoyng CB, Huang PL, Hveem K, Ikram MA, Ingelsson E, Jackson AU, Jansson JH, Jarvik GP, Jensen GB, Jhun MA, Jia Y, Jiang X, Johansson S, Jørgensen ME, Jørgensen T, Jousilahti P, Jukema JW, Kahali B, Kahn RS, Kähönen M, Kamstrup PR, Kanoni S, Kaprio J, Karaleftheri M, Kardia SL, Karpe F, Kee F, Keeman R, Kiemeney LA, Kitajima H, Kluivers KB, Kocher T, Komulainen P, Kontto J, Kooner JS, Kooperberg C, Kovacs P, Kriebel J, Kuivaniemi H, Küry S, Kuusisto J, La Bianca M, Laakso M, Lakka TA, Lange EM, Lange LA, Langefeld CD, Langenberg C, Larson EB, Lee IT, Lehtimäki T, Lewis CE, Li H, Li J, Li-Gao R, Lin H, Lin LA, Lin X, Lind L, Lindström J, Linneberg A, Liu Y, Liu Y, Lophatananon A, Luan J, Lubitz SA, Lyytikäinen LP, Mackey DA, Madden PA, Manning AK, Männistö S, Marenne G, Marten J, Martin NG, Mazul AL, Meidtner K, Metspalu A, Mitchell P, Mohlke KL, Mook-Kanamori DO, Morgan A, Morris AD, Morris AP, Müller-Nurasyid M, Munroe PB, Nalls MA, Nauck M, Nelson CP, Neville M, Nielsen SF, Nikus K, Njølstad PR, Nordestgaard BG, Ntalla I, O'Connel JR, Oksa H, Loohuis LM, Ophoff RA, Owen KR, Packard CJ, Padmanabhan S, Palmer CN, Pasterkamp G, Patel AP, Pattie A, Pedersen O, Peissig PL, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JR, Person TN, Pirie A, Polasek O, Posthuma D, Raitakari OT, Rasheed A, Rauramaa R, Reilly DF, Reiner AP, Renström F, Ridker PM, Rioux JD, Robertson N, Robino A, Rolandsson O, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Sandow K, Sapkota Y, Sattar N, Schmidt MK, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe MP, Shah S, Sim X, Sivapalaratnam S, Small KS, Smith AV, Smith JA, Southam L, Spector TD, Speliotes EK, Starr JM, Steinthorsdottir V, Stringham HM, Stumvoll M, Surendran P, 't Hart LM, Tansey KE, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorsteinsdottir U, Thuesen BH, Tönjes A, Tromp G, Trompet S, Tsafantakis E, Tuomilehto J, Tybjaerg-Hansen A, Tyrer JP, Uher R, Uitterlinden AG, Ulivi S, van der Laan SW, Van Der Leij AR, van Duijn CM, van Schoor NM, van Setten J, Varbo A, Varga TV, Varma R, Edwards DR, Vermeulen SH, Vestergaard H, Vitart V, Vogt TF, Vozzi D, Walker M, Wang F, Wang CA, Wang S, Wang Y, Wareham NJ, Warren HR, Wessel J, Willems SM, Wilson JG, Witte DR, Woods MO, Wu Y, Yaghootkar H, Yao J, Yao P, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zhao W, Zheng H, Zhou W, Rotter JI, Boehnke M, Kathiresan S, McCarthy MI, Willer CJ, Stefansson K, Borecki IB, Liu DJ, North KE, Heard-Costa NL, Pers TH, Lindgren CM, Oxvig C, Kutalik Z, Rivadeneira F, Loos RJ, Frayling TM, Hirschhorn JN, Deloukas P, and Lettre G
Subjects: ADAMTS Proteins genetics, Adult, Alleles, Cell Adhesion Molecules genetics, Female, Genome, Human genetics, Glycoproteins genetics, Glycoproteins metabolism, Glycosaminoglycans biosynthesis, Hedgehog Proteins genetics, Humans, Intercellular Signaling Peptides and Proteins genetics, Intercellular Signaling Peptides and Proteins metabolism, Interferon Regulatory Factors genetics, Interleukin-11 Receptor alpha Subunit genetics, Male, Multifactorial Inheritance genetics, NADPH Oxidase 4, NADPH Oxidases genetics, Phenotype, Pregnancy-Associated Plasma Protein-A metabolism, Procollagen N-Endopeptidase genetics, Proteoglycans biosynthesis, Proteolysis, Receptors, Androgen genetics, Somatomedins metabolism, Body Height genetics, Gene Frequency genetics, Genetic Variation genetics
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
Published: 2017
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26. Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility.

Author: Lamparter D, Marbach D, Rueedi R, Bergmann S, and Kutalik Z
Subjects: Binding Sites genetics, Cell Line, Chromatin metabolism, Chromatin Immunoprecipitation, Computational Biology, Humans, Transcription Factors metabolism, Chromatin chemistry, Chromatin genetics, Genome-Wide Association Study, Transcription Factors genetics
Abstract: To better understand genome regulation, it is important to uncover the role of transcription factors in the process of chromatin structure establishment and maintenance. Here we present a data-driven approach to systematically characterise transcription factors that are relevant for this process. Our method uses a linear mixed modelling approach to combine datasets of transcription factor binding motif enrichments in open chromatin and gene expression across the same set of cell lines. Applying this approach to the ENCODE dataset, we confirm already known and imply numerous novel transcription factors that play a role in the establishment or maintenance of open chromatin. In particular, our approach rediscovers many factors that have been annotated as pioneer factors., Competing Interests: The authors have declared that no competing interests exist.
Published: 2017
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27. [ 18 F]Fluoro-azomycin-2´-deoxy-β-d-ribofuranoside - A new imaging agent for tumor hypoxia in comparison with [ 18 F]FAZA.

Author: Schweifer A, Maier F, Ehrlichmann W, Lamparter D, Kneilling M, Pichler BJ, Hammerschmidt F, and Reischl G
Subjects: Animals, Cell Line, Tumor, Female, Mice, Radiochemistry, Tissue Distribution, Nitroimidazoles chemistry, Nitroimidazoles pharmacokinetics, Nucleosides chemistry, Nucleosides pharmacokinetics, Positron-Emission Tomography methods, Tumor Hypoxia
Abstract: Introduction: Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [ 18 F]Fluoro-azomycin-α-arabinoside ([ 18 F]FAZA) - already in clinical use - may be seen as α-configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside transporters. To enhance image contrast in comparison to [ 18 F]FAZA our objective was to 18 F-radiolabel an azomycin-2´-deoxyriboside with β-configuration ([ 18 F]FAZDR, [ 18 F]-β-8) to mimic nucleosides more closely and comparatively evaluate it versus [ 18 F]FAZA., Methods: Precursor and cold standards for [ 18 F]FAZDR were synthesized from methyl 2-deoxy-d-ribofuranosides α- and β-1 in 6 steps yielding precursors α- and β-5. β-5 was radiolabeled in a GE TRACERlab FX F-N synthesizer in DMSO and deprotected with NH 4 OH to give [ 18 F]FAZDR ([ 18 F]-β-8). [ 18 F]FAZA or [ 18 F]FAZDR was injected in BALB/c mice bearing CT26 colon carcinoma xenografts, PET scans (10min) were performed after 1, 2 and 3h post injection (p.i.). On a subset of mice injected with [ 18 F]FAZDR, we analyzed biodistribution., Results: [ 18 F]FAZDR was obtained in non-corrected yields of 10.9±2.4% (9.1±2.2GBq, n=4) 60min EOB, with radiochemical purity >98% and specific activity >50GBq/μmol. Small animal PET imaging showed a decrease in uptake over time for both [ 18 F]FAZDR (1h p.i.: 0.56±0.22% ID/cc, 3h: 0.17±0.08% ID/cc, n=9) and [ 18 F]FAZA (1h: 1.95±0.59% ID/cc, 3h: 0.87±0.55% ID/cc), whereas T/M ratios were significantly higher for [ 18 F]FAZDR at 1h (2.76) compared to [ 18 F]FAZA (1.69, P<0.001), 3h p.i. ratios showed no significant difference. Moreover, [ 18 F]FAZDR showed an inverse correlation between tracer uptake in carcinomas and oxygen breathing, while muscle tissue uptake was not affected by switching from air to oxygen., Conclusions: First PET imaging results with [ 18 F]FAZDR showed advantages over [ 18 F]FAZA regarding higher tumor contrast at earlier time points p.i. Availability of precursor and cold fluoro standard together with high output radiosynthesis will allow for a more detailed quantitative evaluation of [ 18 F]FAZDR, especially with regard to mechanistic studies whether active transport processes are involved, compared to passive diffusion as observed for [ 18 F]FAZA., (Copyright © 2016 Elsevier Inc. All rights reserved.)
Published: 2016
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28. Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

Author: Marbach D, Lamparter D, Quon G, Kellis M, Kutalik Z, and Bergmann S
Subjects: Genetic Variation genetics, Genome, Human, Genome-Wide Association Study, Humans, Organ Specificity, Promoter Regions, Genetic genetics, Protein Interaction Mapping methods, Transcription Factors genetics, Brain Diseases genetics, Brain Diseases metabolism, Cell Lineage genetics, Computational Biology methods, Epigenomics, Gene Regulatory Networks, Transcription Factors metabolism
Abstract: Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants--including variants that do not reach genome-wide significance--often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).
Published: 2016
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29. Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.

Author: Lamparter D, Marbach D, Rueedi R, Kutalik Z, and Bergmann S
Subjects: HapMap Project, Humans, Phenotype, Software, Algorithms, Computational Biology methods, Genome-Wide Association Study methods, Polymorphism, Single Nucleotide genetics
Abstract: Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries.
Published: 2016
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30. Genome-Wide Analysis Reveals Novel Regulators of Growth in Drosophila melanogaster.

Author: Vonesch SC, Lamparter D, Mackay TF, Bergmann S, and Hafen E
Subjects: Animals, Drosophila melanogaster growth & development, Humans, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci genetics, Signal Transduction, Body Size genetics, Drosophila melanogaster genetics, Genetic Variation, Genome-Wide Association Study
Abstract: Organismal size depends on the interplay between genetic and environmental factors. Genome-wide association (GWA) analyses in humans have implied many genes in the control of height but suffer from the inability to control the environment. Genetic analyses in Drosophila have identified conserved signaling pathways controlling size; however, how these pathways control phenotypic diversity is unclear. We performed GWA of size traits using the Drosophila Genetic Reference Panel of inbred, sequenced lines. We find that the top associated variants differ between traits and sexes; do not map to canonical growth pathway genes, but can be linked to these by epistasis analysis; and are enriched for genes and putative enhancers. Performing GWA on well-studied developmental traits under controlled conditions expands our understanding of developmental processes underlying phenotypic diversity.
Published: 2016
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31. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

Author: Hoggart CJ, Venturini G, Mangino M, Gomez F, Ascari G, Zhao JH, Teumer A, Winkler TW, Tšernikova N, Luan J, Mihailov E, Ehret GB, Zhang W, Lamparter D, Esko T, Macé A, Rüeger S, Bochud PY, Barcella M, Dauvilliers Y, Benyamin B, Evans DM, Hayward C, Lopez MF, Franke L, Russo A, Heid IM, Salvi E, Vendantam S, Arking DE, Boerwinkle E, Chambers JC, Fiorito G, Grallert H, Guarrera S, Homuth G, Huffman JE, Porteous D, Moradpour D, Iranzo A, Hebebrand J, Kemp JP, Lammers GJ, Aubert V, Heim MH, Martin NG, Montgomery GW, Peraita-Adrados R, Santamaria J, Negro F, Schmidt CO, Scott RA, Spector TD, Strauch K, Völzke H, Wareham NJ, Yuan W, Bell JT, Chakravarti A, Kooner JS, Peters A, Matullo G, Wallaschofski H, Whitfield JB, Paccaud F, Vollenweider P, Bergmann S, Beckmann JS, Tafti M, Hastie ND, Cusi D, Bochud M, Frayling TM, Metspalu A, Jarvelin MR, Scherag A, Smith GD, Borecki IB, Rousson V, Hirschhorn JN, Rivolta C, Loos RJ, and Kutalik Z
Subjects: Adult, Body Mass Index, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomic Imprinting, Genotype, Humans, Male, Obesity pathology, White People genetics, Glucose Transport Proteins, Facilitative genetics, Obesity genetics, Polymorphism, Single Nucleotide genetics, Potassium Channels, Tandem Pore Domain genetics
Abstract: The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.
Published: 2014
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32. Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals.

Author: Kuntzsch M, Lamparter D, Brüggener N, Müller M, Kienzle GJ, and Reischl G
Abstract: Kryptofix® 2.2.2 (Kry) or tetrabutylammonium (TBA) are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET). Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration of residual reagent is not reached. Here, we describe the successful development and pharmaceutical validation (for specificity, accuracy and detection limit) of a simplified color spot test on TLC plates. We were able to prove its applicability as a general, time and resources saving, easy to handle and reliable method in daily routine analyzing 18F-tracer formulations for Kry (in [18F]FDG or [18F]FECh) or TBA contaminations (in [18F]FLT) with special regard to complex matrix compositions.
Published: 2014
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33. In vivo imaging of cell proliferation enables the detection of the extent of experimental rheumatoid arthritis by 3'-deoxy-3'-18f-fluorothymidine and small-animal PET.

Author: Fuchs K, Kohlhofer U, Quintanilla-Martinez L, Lamparter D, Kötter I, Reischl G, Röcken M, Pichler BJ, and Kneilling M
Subjects: Animals, Arthritis, Rheumatoid chemically induced, Arthritis, Rheumatoid metabolism, Biological Transport, Cell Proliferation, Feasibility Studies, Female, Gene Expression Regulation, Glucose-6-Phosphate Isomerase adverse effects, Ki-67 Antigen metabolism, Magnetic Resonance Imaging, Mice, Mice, Inbred BALB C, Multimodal Imaging, Tomography, X-Ray Computed, Arthritis, Rheumatoid diagnostic imaging, Arthritis, Rheumatoid pathology, Dideoxynucleosides metabolism, Positron-Emission Tomography
Abstract: Unlabelled: The aim of this work was to study the feasibility of measuring cell proliferation noninvasively in vivo during different stages of experimental arthritis using the PET proliferation tracer 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT)., Methods: We injected mice with serum containing glucose-6-phosphate-isomerase-specific antibodies to induce experimental arthritis, and we injected control mice with control serum. Animals injected with (18)F-FLT 1, 3, 6, and 8 d after the onset of disease were analyzed in vivo by PET, PET/CT, or PET/MR imaging followed by autoradiography analysis. The (18)F-FLT uptake in the ankles and forepaws was quantified on the basis of the PET images by drawing standardized regions of interest. To correlate the in vivo PET data with cell proliferation, we performed Ki-67 immunohistochemistry of diseased and healthy joints at the corresponding time points., Results: Analysis of the different stages of arthritic joint disease revealed enhanced (18)F-FLT uptake in arthritic ankles (2.2 ± 0.2 percentage injected dose per gram [%ID/g]) and forepaws (2.1 ± 0.3 %ID/g), compared with healthy ankles (1.4 ± 0.3 %ID/g) and forepaws (1.5 ± 0.5 %ID/g), as early as 1 d after the glucose-6-phosphate-isomerase serum injection, a time point characterized by clear histologic signs of arthritis but only slight ankle swelling. The (18)F-FLT uptake in the ankles (3.5 ± 0.3 %ID/g) reached the maximum observed level at day 8. Ki-67 immunohistochemical staining of the arthritic ankles and forepaws revealed a strong correlation with the in vivo (18)F-FLT PET data. PET/CT and PET/MR imaging measurements enabled us to identify whether the (18)F-FLT uptake was located in the bone or the soft tissue., Conclusion: Noninvasive in vivo measurement of cell proliferation in experimental arthritis using (18)F-FLT PET is a promising tool to investigate the extent of arthritic joint inflammation.
Published: 2013
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34. A multi-SNP locus-association method reveals a substantial fraction of the missing heritability.

Author: Ehret GB, Lamparter D, Hoggart CJ, Whittaker JC, Beckmann JS, and Kutalik Z
Subjects: Body Mass Index, Humans, Lipids blood, Lipids genetics, Phenotype, Waist-Hip Ratio, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract: There are many known examples of multiple semi-independent associations at individual loci; such associations might arise either because of true allelic heterogeneity or because of imperfect tagging of an unobserved causal variant. This phenomenon is of great importance in monogenic traits but has not yet been systematically investigated and quantified in complex-trait genome-wide association studies (GWASs). Here, we describe a multi-SNP association method that estimates the effect of loci harboring multiple association signals by using GWAS summary statistics. Applying the method to a large anthropometric GWAS meta-analysis (from the Genetic Investigation of Anthropometric Traits consortium study), we show that for height, body mass index (BMI), and waist-to-hip ratio (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be explained on top of the previously reported 10% (height), 1.5% (BMI), and 1% (WHR). The method also permitted a substantial increase (by up to 50%) in the number of loci that replicate in a discovery-validation design. Specifically, we identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains significantly more variance than does the best individual SNP. A detailed analysis of multi-SNPs shows that most of the additional variability explained is derived from SNPs that are not in linkage disequilibrium with the lead SNP, suggesting a major contribution of allelic heterogeneity to the missing heritability., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Published: 2012
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35. Single-cell analysis of population context advances RNAi screening at multiple levels.

Author: Snijder B, Sacher R, Rämö P, Liberali P, Mench K, Wolfrum N, Burleigh L, Scott CC, Verheije MH, Mercer J, Moese S, Heger T, Theusner K, Jurgeit A, Lamparter D, Balistreri G, Schelhaas M, De Haan CA, Marjomäki V, Hyypiä T, Rottier PJ, Sodeik B, Marsh M, Gruenberg J, Amara A, Greber U, Helenius A, and Pelkmans L
Subjects: Bayes Theorem, Cellular Microenvironment, Computer Simulation, Genomics methods, HeLa Cells, Humans, Image Processing, Computer-Assisted methods, Models, Biological, RNA, Small Interfering, RNA, Viral isolation & purification, Reproducibility of Results, Systems Biology methods, Viral Proteins genetics, Viral Proteins isolation & purification, Virus Diseases metabolism, Viruses isolation & purification, Viruses pathogenicity, RNA Interference, Single-Cell Analysis methods, Virus Diseases genetics
Abstract: Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single-cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome-wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell-based screens at this depth reveals widespread RNAi-induced changes in the population context of individual cells leading to indirect RNAi effects, as well as perturbations of cell-to-cell variability regulators. We find that accounting for indirect effects improves the consistency between siRNAs targeted against the same gene, and between replicate RNAi screens performed in different cell lines, in different labs, and with different siRNA libraries. In an era where large-scale RNAi screens are increasingly performed to reach a systems-level understanding of cellular processes, we show that this is often improved by analyses that account for and incorporate the single-cell microenvironment.
Published: 2012
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35 results on '"Lamparter D"'

1. Assessment of network module identification across complex diseases

2. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (Nature Genetics, (2018), 50, 1, (26-41), 10.1038/s41588-017-0011-x)

3. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)

4. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

5. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

6. Rare and low-frequency coding variants alter human adult height

7. Rare and low-frequency coding variants alter human adult height

8. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

9. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index

10. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.

11. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

12. Local regulatory networks across two tissues and applications to analyze rare non-coding variants

13. Assessment of network module identification across complex diseases

14. Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.

15. Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency.

16. A framework for integrating directed and undirected annotations to build explanatory models of cis-eQTL data.

17. Assessment of network module identification across complex diseases.

18. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

19. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

20. Improved small scale production of iodine-124 for radiolabeling and clinical applications.

21. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

22. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

23. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

24. Metabomatching: Using genetic association to identify metabolites in proton NMR spectroscopy.

25. Rare and low-frequency coding variants alter human adult height.

26. Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility.

27. [ 18 F]Fluoro-azomycin-2´-deoxy-β-d-ribofuranoside - A new imaging agent for tumor hypoxia in comparison with [ 18 F]FAZA.

28. Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

29. Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.

30. Genome-Wide Analysis Reveals Novel Regulators of Growth in Drosophila melanogaster.

31. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

32. Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals.

33. In vivo imaging of cell proliferation enables the detection of the extent of experimental rheumatoid arthritis by 3'-deoxy-3'-18f-fluorothymidine and small-animal PET.

34. A multi-SNP locus-association method reveals a substantial fraction of the missing heritability.

35. Single-cell analysis of population context advances RNAi screening at multiple levels.

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35 results on '"Lamparter D"'

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