Nature genetics · 2011

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Trynka Gosia, Hunt Karen A, Bockett Nicholas A, Romanos Jihane, Mistry Vanisha, Szperl Agata, Bakker Sjoerd F, Bardella Maria Teresa, Bhaw-Rosun Leena, Castillejo Gemma, de la Concha Emilio G, de Almeida Rodrigo Coutinho, Dias Kerith-Rae M, van Diemen Cleo C, Dubois Patrick C A, Duerr Richard H, Edkins Sarah, Franke Lude, Fransen Karin, Gutierrez Javier, Heap Graham A R, Hrdlickova Barbara, Hunt Sarah, Plaza Izurieta Leticia, Izzo Valentina, Joosten Leo A B, Langford Cordelia, Mazzilli Maria Cristina, Mein Charles A, Midah Vandana, Mitrovic Mitja, Mora Barbara, Morelli Marinita, Nutland Sarah, Núñez Concepción, Onengut-Gumuscu Suna, Pearce Kerra, Platteel Mathieu, Polanco Isabel, Potter Simon, Ribes-Koninckx Carmen, Ricaño-Ponce Isis, Rich Stephen S, Rybak Anna, Santiago José Luis, Senapati Sabyasachi, Sood Ajit, Szajewska Hania, Troncone Riccardo, Varadé Jezabel, Wallace Chris, Wolters Victorien M, Zhernakova Alexandra, Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), PreventCD Study Group, Wellcome Trust Case Control Consortium (WTCCC), Thelma B K, Cukrowska Bozena, Urcelay Elena, Bilbao Jose Ramon, Mearin M Luisa, Barisani Donatella, Barrett Jeffrey C, Plagnol Vincent, Deloukas Panos, Wijmenga Cisca, van Heel David A

Аннотация

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.

Предметные рубрики MeSH

Case-Control Studies Celiac Disease Chromosome Mapping Gene Frequency Genetic Loci Genome-Wide Association Study Haplotypes Humans Linkage Disequilibrium Polymorphism, Single Nucleotide Risk Factors

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH