| dc.contributor.author | Mc Manus, Ross | en |
| dc.contributor.author | Kelleher, Dermot | en |
| dc.date.accessioned | 2010-12-14T09:55:36Z | |
| dc.date.available | 2010-12-14T09:55:36Z | |
| dc.date.issued | 2010 | en |
| dc.date.submitted | 2010 | en |
| dc.identifier.citation | Dubois PCA, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GA, ?d?ny R, Aromaa A, Bardella MT, van den Berg LH, Bockett NA, de la Concha EG, Dema B, Fehrmann RS, Fern?ndez-Arquero M, Fiatal S, Grandone E, Green PM, Groen HJ, Gwilliam R, Houwen RH, Hunt SE, Kaukinen K, Kelleher D, Korponay-Szabo I, Kurppa K, MacMathuna P, M?ki M, Mazzilli MC, McCann OT, Mearin ML, Mein CA, Mirza MM, Mistry V, Mora B, Morley KI, Mulder CJ, Murray JA, N??ez C, Oosterom E, Ophoff RA, Polanco I, Peltonen L, Platteel M, Rybak A, Salomaa V, Schweizer JJ, Sperandeo MP, Tack GJ, Turner G, Veldink JH, Verbeek, Weersma RK, Wolters VM, Urcelay E, Cukrowska B, Greco L, Neuhausen SL, McManus R, Barisani D, Deloukas P, Barrett JC, Saavalainen P, Wijmenga C, van Heel DA, Multiple common variants for celiac disease influencing immune gene expression, Nature Genetics, 42, 4, 2010, 295 - 302 | en |
| dc.identifier.other | Y | en |
| dc.description | PUBLISHED | en |
| dc.description.abstract | We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression. | en |
| dc.description.sponsorship | We thank Celiac UK for assistance with direct recruitment of celiac disease individuals, and UK clinicians (L.C. Dinesen, G.K.T. Holmes, P.D. Howdle, J.R.F. Walters, D.S. Sanders, J. Swift, R. Crimmins, P. Kumar, D.P. Jewell, S.P.L. Travis, K. Moriarty) who recruited celiac disease blood samples described in our previous studies1,22. We thank the genotyping facility of the UMCG (J. Smolonska, P. van der Vlies) for generating part of the GWAS and replication data and the gene expression data; R. Booij and M. Weenstra are thanked for preparation of Italian samples. H. Ahola, A. Heimonen, L. Koskinen, E. Einarsdottir and K. Loytynoja are thanked for their work on Finnish sample collection, preparation and data handling, and E. Szathmari, J.B.Kovacs, M. Lorincz and A. Nagy for their work with the Hungarian families. Health2000 organization, Finrisk consortium, K. Mustalahti, M. Perola, K. Kristiansson and J. Koskinen are thanked for providing the Finnish control genotypes. We thank D.G. Clayton and N. Walker for providing T1DGC data in the required format. We thank the Irish Transfusion Service and Trinity College Dublin Biobank for control samples; V. Trimble, E. Close, G. Lawlor, A. Ryan, M. Abuzakouk, C. O?Morain, G. Horgan, for celiac sample collection and preparation We acknowledge DNA provided by Mayo Clinic Rochester, and Prof. M. Bonamico and Prof. M. Barbato (Department of Paediatrics, Sapienza University of Rome, Italy) for recruiting individuals. We thank Polish clinicians for recruitment of celiac disease individuals (Z. Domagala, A. Szaflarska-Poplawska, B. Oralewska, W. Cichy, B. Korczowski, K. Fryderek, E. Hapyn, K. Karczewska, A. Zalewska, I. Sakowska-Maliszewska, R. Mozrzymas, A. Zabka, M. Kolasa, B. Iwanczak). We thank M. Szperl for isolating DNA from blood samples provided by Children?s Memorial Health Institute (Warsaw, Poland).
Dutch and UK genotyping for the second celiac disease GWAS was funded by the Wellcome Trust (084743 to D.A.vH.). Italian genotyping for the second celiac disease GWAS was funded by the Coeliac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009 to C.W.) and by the Netherlands Organisation for Scientific Research (NWO, VICI grant 918.66.620 to C.W.). E.G. is funded by the Italian Ministry of Healthy (grant RC2009). L.H.v.d.B. acknowledges funding from the Prinses Beatrix Fonds, the Adessium foundation, and the Amyotrophic Lateral Sclerosis Association. L.F. received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135). P.C.D. is a MRC Clinical Training Fellow (G0700545). G.T. received a Ter Meulen Fund grant from the Royal Netherlands Academy of Arts and Sciences (KNAW). The gene expression study was funded in part by COPACETIC (EU grant 201379). This study makes use of data generated by the Wellcome Trust Case-Control Consortium 2 (WTCCC2). A full list of the WTCCC2 investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the WTCCC2 project was provided by the Wellcome Trust under award 085475. This research utilizes resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. We acknowledge the use of BRC Core Facilities provided by the financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy?s & St Thomas? NHS Foundation Trust in partnership with King?s College London and King?s College Hospital NHS Foundation Trust. We acknowledge funding from NIH: DK050678 and DK081645 (to S.L.N.), NS058980 (to R.A.O.); DK57892 and DK071003 (to J.A.M.). Collection of Finnish and Hungarian patients was funded by EU Commission (MEXT-CT-2005-025270), the Academy of Finland, Hungarian Scientific Research Fund (contract OTKA 61868), the University of Helsinki Funds, the Competitive Research Funding of the Tampere University Hospital, the Foundation of Pediatric Research, Sigrid Juselius Foundation, and the Hungarian Academy of Sciences (2006TKI247 to RA). Funding for the Polish samples collection and genotyping was provided by UMC Cooperation Project (6/06/2006/NDON). R.McM is funded by Science Foundation Ireland. C. Nu?ez has a FIS contract (CP08/0213). The Dublin Centre for Clinical Research contributed to patient sample collection and is funded by the Irish Health Research Board and the Wellcome Trust
Finally we thank all individuals with celiac disease and control individuals for participating in this study. | en |
| dc.format.extent | 295 | en |
| dc.format.extent | 302 | en |
| dc.language.iso | en | en |
| dc.relation.ispartofseries | Nature Genetics | en |
| dc.relation.ispartofseries | 42 | en |
| dc.relation.ispartofseries | 4 | en |
| dc.rights | Y | en |
| dc.subject | Genetics | en |
| dc.subject | celiac risk variants | en |
| dc.title | Multiple common variants for celiac disease influencing immune gene expression | en |
| dc.type | Journal Article | en |
| dc.type.supercollection | scholarly_publications | en |
| dc.type.supercollection | refereed_publications | en |
| dc.identifier.peoplefinderurl | http://people.tcd.ie/rmcmanus | en |
| dc.identifier.peoplefinderurl | http://people.tcd.ie/kellehdp | en |
| dc.identifier.rssinternalid | 64494 | en |
| dc.identifier.doi | http://dx.doi.org/10.1038/ng.543 | en |
| dc.subject.TCDTheme | Genes & Society | en |
| dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
| dc.subject.TCDTheme | International Development | en |
| dc.identifier.rssuri | http://dx.doi.org/10.1038/ng.54 | en |
| dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
| dc.identifier.uri | http://hdl.handle.net/2262/41272 | |
