Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease
| Autor: | Trynka, G., Hunt, K.A., Bockett, N.A., Romanos, J., Mistry, V., Szperl, A., Bakker, S.F., Bardella, M.T., Bhaw-Rosun, L., Castillejo, G., Concha, E.G. de la, Almeida, R.C. de, Dias, K.R.M., Diemen, C.C. van, Dubois, P.C.A., Duerr, R.H., Edkins, S., Franke, L., Fransen, K., Gutierrez, J., Heap, G.A.R., Hrdlickova, B., Hunt, S., Izurieta, L.P., Izzo, V., Joosten, L.A.B., Langford, C., Mazzilli, M.C., Mein, C.A., Midah, V., Mitrovic, M., Mora, B., Morelli, M., Nutland, S., Nunez, C., Onengut-Gumuscu, S., Pearce, K., Platteel, M., Polanco, I., Potter, S., Ribes-Koninckx, C., Ricano-Ponce, I., Rich, S.S., Rybak, A., Santiago, J.L., Senapati, S., Sood, A., Szajewska, H., Troncone, R., Varade, J., Wallace, C., Wolters, V.M., Zhernakova, A., Thelma, B.K., Cukrowska, B., Urcelay, E., Bilbao, J.R., Mearin, M.L., Barisani, D., Barrett, J.C., Plagnol, V., Deloukas, P., Wijmenga, C., Heel, D.A. van, Spanish Consortium Genetics Coelia, PreventCD Study Grp, WTCCC |
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| Přispěvatelé: | Trynka, G, Hunt, K, Bockett, N, Romanos, J, Mistry, V, Szperl, A, Bakker, S, Bardella, M, Bhaw Rosun, L, Castillejo, G, De la Concha, E, De Almeida, R, Dias, K, Van Diemen, C, Dubois, P, Duerr, R, Edkins, S, Franke, L, Fransen, K, Gutierrez, J, Heap, G, Hrdlickova, B, Hunt, S, Izurieta, L, Izzo, V, Joosten, L, Langford, C, Mazzilli, M, Mein, C, Midah, V, Mitrovic, M, Mora, B, Morelli, M, Nutland, S, Núñez, C, Onengut Gumuscu, S, Pearce, K, Platteel, M, Polanco, I, Potter, S, Ribes Koninckx, C, Ricaño Ponce, I, Rich, S, Rybak, A, Santiago, J, Senapati, S, Sood, A, Szajewska, H, Troncone, R, Varadé, J, Wallace, C, Wolters, V, Zhernakova, A, Spanish Consortium on the Genetics of Coeliac, D, PreventCD Study, G, Wellcome Trust Case Control, C, Thelma, B, Cukrowska, B, Urcelay, E, Bilbao, J, Mearin, M, Barisani, D, Barrett, J, Plagnol, V, Deloukas, P, Wijmenga, C, Van Heel, D, Gastroenterology and hepatology, CCA - Disease profiling, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
EXPRESSION
Linkage disequilibrium Population LOCI Genome-wide association study Locus (genetics) Human leukocyte antigen Biology PHENOTYPE Polymorphism Single Nucleotide Linkage Disequilibrium REGION 03 medical and health sciences 0302 clinical medicine Gene Frequency Risk Factors Genetics RISK VARIANTS Humans 1000 Genomes Project GENOME-WIDE ASSOCIATION education Genotyping POPULATION 030304 developmental biology 0303 health sciences education.field_of_study celiac disease GWAS LARGE-SCALE BIO/13 - BIOLOGIA APPLICATA Chromosome Mapping Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1] GENE Genetic architecture Celiac Disease Haplotypes Genetic Loci 030220 oncology & carcinogenesis Case-Control Studies MAP Genome-Wide Association Study |
| Zdroj: | Nature Genetics, 43(12), 1193-U45 Nature Genetics, 43(12), 1193-1201. Nature Publishing Group NATURE GENETICS r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname Trynka, G, Hunt, K A, Bockett, N A, Romanos, J, Mistry, V, Szperl, A, Bakker, S F, Bardella, M T, Bhaw-Rosun, L, Castillejo, G, de la Concha, E G, de Almeida, R C, Dias, K R M, van Diemen, C C, Dubois, P C A, Duerr, R H, Edkins, S, Franke, L, Fransen, K, Gutierrez, J, Heap, G A R, Hrdlickova, B, Hunt, S, Izurieta, L P, Izzo, V, Joosten, L A B, Langford, C, Mazzilli, M C, Mein, C A, Midah, V, Mitrovic, M, Mora, B, Morelli, M, Nutland, S, Nunez, C, Onengut-Gumuscu, S, Pearce, K, Platteel, M, Polanco, I, Potter, S, Ribes-Koninckx, C, Ricano-Ponce, I, Rich, S S, Rybak, A, Santiago, J L, Senapati, S, Sood, A, Szajewska, H, Troncone, R, Varade, J, Wallace, C, Wolters, V M, Zhernakova, A, Thelma, B K, Cukrowska, B, Urcelay, E, Bilbao, J R, Mearin, M L, Barisani, D, Barrett, J C, Plagnol, V, Deloukas, P, Wijmenga, C & van Heel, D A 2011, ' Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease ', Nature Genetics, vol. 43, no. 12, pp. 1193-1201 . https://doi.org/10.1038/ng.998 Nature Genetics, 43, 12, pp. 1193-201 Nature Genetics, 43(12), 1193-U45. Nature Publishing Group Nature Genetics, 43, 1193-201 |
| ISSN: | 1061-4036 |
| DOI: | 10.1038/ng.998 |
| Popis: | Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease. © 2011 Nature America, Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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