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PubMed ID:
22057235
Public Release Type:
Journal
Publication Year: 2011
Affiliation: Genetics Department, University Medical Center and University of Groningen, The Netherlands.
DOI:
https://doi.org/10.1038/ng.998
Authors:
Barrett JC,
Midah V,
Mein CA,
Mazzilli MC,
Langford C,
Joosten LA,
Izzo V,
Plaza Izurieta L,
Hunt S,
Hrdlickova B,
Heap GA,
Gutierrez J,
Fransen K,
Franke L,
Edkins S,
Duerr RH,
Dubois PC,
van Diemen CC,
Dias KR,
de Almeida RC,
de la Concha EG,
Castillejo G,
Bhaw-Rosun L,
Bardella MT,
Bakker SF,
Szperl A,
Mistry V,
Romanos J,
Bockett NA,
Hunt KA,
Trynka G,
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,
Plagnol V,
Deloukas P,
Wijmenga C,
van Heel DA,
Mitrovic M,
Pearce K,
Platteel M,
Polanco I,
Potter S,
Ribes-Koninckx C,
Ricaño-Ponce I,
Mora B,
Morelli M,
Nutland S,
Núñez C,
Onengut-Gumuscu S
Studies:
Type 1 Diabetes Genetics Consortium
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.
