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Publication Information

PubMed ID
Public Release Type
Journal
Publication Year
2011
Affiliation
Genetics Department, University Medical Center and University of Groningen, The Netherlands.
Authors
Bakker SF, Bardella MT, Barisani D, Barrett JC, Bhaw-Rosun L, Bilbao JR, Bockett NA, Castillejo G, Cukrowska B, de Almeida RC, de la Concha EG, Deloukas P, Dias KR, Dubois PC, Duerr RH, Edkins S, Franke L, Fransen K, Gutierrez J, Heap GA, Hrdlickova B, Hunt KA, Hunt S, Izzo V, Joosten LA, Langford C, Mazzilli MC, Mearin ML, Mein CA, Midah V, Mistry V, Mitrovic M, Mora B, Morelli M, Núñez C, Nutland S, Onengut-Gumuscu S, Pearce K, Plagnol V, Platteel M, Plaza Izurieta L, Polanco I, Potter S, PreventCD Study Group, Ribes-Koninckx C, Ricaño-Ponce I, Rich SS, Romanos J, Rybak A, Santiago JL, Senapati S, Sood A, Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), Szajewska H, Szperl A, Thelma BK, Troncone R, Trynka G, Urcelay E, van Diemen CC, van Heel DA, Varadé J, Wallace C, Wellcome Trust Case Control Consortium (WTCCC), Wijmenga C, Wolters VM, Zhernakova A
Studies
Citation
Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, Bakker SF, Bardella MT, Bhaw-Rosun L, Castillejo G, de la Concha EG, de Almeida RC, Dias KR, van Diemen CC, Dubois PC, Duerr RH, Edkins S, Franke L, Fransen K, Gutierrez J, Heap GA, Hrdlickova B, Hunt S, Plaza Izurieta L, Izzo V, Joosten LA, Langford C, Mazzilli MC, Mein CA, 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 SS, Rybak A, Santiago JL, Senapati S, Sood A, Szajewska H, Troncone R, Varadé J, Wallace C, Wolters VM, Zhernakova A, Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), PreventCD Study Group, Wellcome Trust Case Control Consortium (WTCCC), Thelma BK, Cukrowska B, Urcelay E, Bilbao JR, Mearin ML, Barisani D, Barrett JC, Plagnol V, Deloukas P, Wijmenga C, van Heel DA. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet 2011 Nov 6;43(12):1193-201.

Abstract

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.