DOI: 10.1038/ng.998

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Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Gosia Trynka,Karen A. Hunt,Nicholas Bockett,Jihane Romanos,Vanisha Mistry,Agata Szperl,Sjoerd F. Bakker,Maria Teresa Bardella,Leena Bhaw-Rosun,Gemma Castillejo,Emilio G. de la Concha,Rodrigo Coutinho de Almeida,Kerith-Rae Dias,Cleo C. van Diemen,P Dubois,Richard H. Duerr,Sarah Edkins,Lude Franke,Karin Fransén,Javier Gutiérrez,Graham A. Heap,Barbara Hrdličková,Sarah Hunt,Leticia Plaza Izurieta,Valentina Izzo,Leo A. B. Joosten,Cordelia Langford,Maria Cristina Mazzilli,Charles A. Mein,Vandana Midah,Mitja Mitrovič,Barbara Mora,Marinita Morelli,Sarah Nutland,Concepción Núñez,Suna Önengüt-Gümüşcü,Kerra Pearce,Mathieu Platteel,Isabel Polanco,Simon Potter,Carmen Ribes‐Koninckx,Isis Ricaño-Ponce,Stephen S. Rich,Anna Rybak,José Luis Santiago,Sabyasachi Senapati,Ajit Sood,Hania Szajewska,Riccardo Troncone,Jezabel Varadé,Chris Wallace,Victorien M. Wolters,Alexandra Zhernakova,B.K. Thelma,Božena Cukrowská,Elena Urcelay,José Ramón Bilbao,M. Luisa Mearin,Donatella Barisani,Jeffrey C. Barrett,Vincent Plagnol,Panos Deloukas,Cisca Wijmenga,David A. van Heel

Biology

Linkage disequilibrium

Genotyping

2011

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.

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“Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease” is a paper by Gosia Trynka Karen A. Hunt Nicholas Bockett Jihane Romanos Vanisha Mistry Agata Szperl Sjoerd F. Bakker Maria Teresa Bardella Leena Bhaw-Rosun Gemma Castillejo Emilio G. de la Concha Rodrigo Coutinho de Almeida Kerith-Rae Dias Cleo C. van Diemen P Dubois Richard H. Duerr Sarah Edkins Lude Franke Karin Fransén Javier Gutiérrez Graham A. Heap Barbara Hrdličková Sarah Hunt Leticia Plaza Izurieta Valentina Izzo Leo A. B. Joosten Cordelia Langford Maria Cristina Mazzilli Charles A. Mein Vandana Midah Mitja Mitrovič Barbara Mora Marinita Morelli Sarah Nutland Concepción Núñez Suna Önengüt-Gümüşcü Kerra Pearce Mathieu Platteel Isabel Polanco Simon Potter Carmen Ribes‐Koninckx Isis Ricaño-Ponce Stephen S. Rich Anna Rybak José Luis Santiago Sabyasachi Senapati Ajit Sood Hania Szajewska Riccardo Troncone Jezabel Varadé Chris Wallace Victorien M. Wolters Alexandra Zhernakova B.K. Thelma Božena Cukrowská Elena Urcelay José Ramón Bilbao M. Luisa Mearin Donatella Barisani Jeffrey C. Barrett Vincent Plagnol Panos Deloukas Cisca Wijmenga David A. van Heel published in 2011. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.