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

Gosia Trynka; Karen A. Hunt; Nicholas A. 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 M. Dias; Cleo C. van Diemen; Patrick C. A. Dubois; Richard H. Duerr; Sarah Edkins; Lude Franke; Karin Fransen; Javier Gutierrez; Graham A. R. Heap; Barbara Hrdlickova; Sarah Hunt; Leticia Plaza Izurieta; Valentina Izzo; Leo A. B. Joosten; Cordelia Langford; Maria Cristina Mazzilli; Charles A. Mein; Vandana Midah; Mitja Mitrovic; Barbara Mora; Marinita Morelli; Sarah Nutland; Concepcion Nunez; Suna Onengut-Gumuscu; Kerra Pearce; Mathieu Platteel; Isabel Polanco; Simon Potter; Carmen Ribes-Koninckx; Isis Ricano-Ponce; Stephen S. Rich; Anna Rybak; Jose Luis Santiago; Sabyasachi Senapati; Ajit Sood; Hania Szajewska; Riccardo Troncone; Jezabel Varade; Chris Wallace; Victorien M. Wolters; Alexandra Zhernakova; B. K. Thelma; Bozena Cukrowska; Elena Urcelay; Jose Ramon Bilbao; M. Luisa Mearin; Donatella Barisani; Jeffrey C. Barrett; Vincent Plagnol; Panos Deloukas; Cisca Wijmenga; David A. van Heel; Spanish Consortium Genetics Coelia

doi:10.1038/ng.998

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

Journal article

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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 A. Bockett, Jihane Romanos, Vanisha Mistry, Agata Szperl, Sjoerd F. Bakker, Maria Teresa Bardella, Leena Bhaw-Rosun, Gemma Castillejo, …

Nature genetics, Vol.43(12), pp.1193-U45

01/12/2011

DOI: https://doi.org/10.1038/ng.998

PMCID: PMC3242065

PMID: 22057235

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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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Title: Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease
Creators - without role: Gosia Trynka - University Medical Center Groningen
Karen A. Hunt - Queen Mary University of London
Nicholas A. Bockett - Queen Mary University of London
Jihane Romanos - University Medical Center Groningen
Vanisha Mistry - Queen Mary University of London
Agata Szperl - University Medical Center Groningen
Sjoerd F. Bakker - Vrije Universiteit Amsterdam
Maria Teresa Bardella - Ospedale Maggiore
Leena Bhaw-Rosun - Queen Mary University of London
Gemma Castillejo - Hospital Universitari Sant Joan de Reus
Emilio G. de la Concha - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Rodrigo Coutinho de Almeida - University Medical Center Groningen
Kerith-Rae M. Dias - Queen Mary University of London
Cleo C. van Diemen - University of Groningen
Patrick C. A. Dubois - Queen Mary University of London
Richard H. Duerr - University of Pittsburgh
Sarah Edkins - Wellcome Sanger Institute
Lude Franke - University Medical Center Groningen
Karin Fransen - University of Groningen
Javier Gutierrez - University Medical Center Groningen
Graham A. R. Heap - Queen Mary University of London
Barbara Hrdlickova - University Medical Center Groningen
Sarah Hunt - Wellcome Sanger Institute
Leticia Plaza Izurieta - Hosp Cruces, Immunogenet Res Lab, Baracaldo, Bizkaia, Spain
Valentina Izzo - University of Naples Federico II
Leo A. B. Joosten - Radboud University Medical Center
Cordelia Langford - Wellcome Sanger Institute
Maria Cristina Mazzilli - Sapienza University of Rome
Charles A. Mein - Queen Mary University of London
Vandana Midah - Dayanand Medical College & Hospital
Mitja Mitrovic - University Medical Center Groningen
Barbara Mora - Sapienza University of Rome
Marinita Morelli - University of Naples Federico II
Sarah Nutland - Wellcome Trust
Concepcion Nunez - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Suna Onengut-Gumuscu - University of Virginia
Kerra Pearce - Genomics England
Mathieu Platteel - University Medical Center Groningen
Isabel Polanco - Hospital Universitario La Paz
Simon Potter - Wellcome Sanger Institute
Carmen Ribes-Koninckx - Hospital Universitari i Politècnic La Fe
Isis Ricano-Ponce - University Medical Center Groningen
Stephen S. Rich - University of Virginia
Anna Rybak - Children's Memorial Health Institute
Jose Luis Santiago - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Sabyasachi Senapati - University of Delhi
Ajit Sood - Dayanand Medical College & Hospital
Hania Szajewska - Medical University of Warsaw
Riccardo Troncone - University of Naples Federico II
Jezabel Varade - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Chris Wallace - Wellcome Trust
Victorien M. Wolters - University Medical Center Utrecht
Alexandra Zhernakova - Leiden University Medical Center
B. K. Thelma - University of Delhi
Bozena Cukrowska - Children's Memorial Health Institute
Elena Urcelay - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Jose Ramon Bilbao - Hosp Cruces, Immunogenet Res Lab, Baracaldo, Bizkaia, Spain
M. Luisa Mearin - Leiden University
Donatella Barisani - University of Milano-Bicocca
Jeffrey C. Barrett - Wellcome Sanger Institute
Vincent Plagnol - University College London
Panos Deloukas - Wellcome Sanger Institute
Cisca Wijmenga - University Medical Center Groningen
David A. van Heel - Queen Mary University of London
Spanish Consortium Genetics Coelia
Publication Details: Nature genetics, Vol.43(12), pp.1193-U45
Publisher: Springer Nature
Number of pages: 10
Grant note: FIS08/1676; FIS07/0353 / Fondo de Investigacion Sanitaria; Instituto de Salud Carlos III; Spanish Government Council for Scientific and Industrial Research (CSIR), New Dehli, India; Council of Scientific & Industrial Research (CSIR) - India National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) G1001158; G0801418B; G0700545; G0000934; G1001799 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 918.66.620 / Netherlands Organisation for Scientific Research (NWO); Netherlands Organization for Scientific Research (NWO) Netherlands Genomics Initiative G0000934 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 1R01CA141743; U01-DK062418 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA G1001799; G1001158; G0700545; G0000934 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 084743; 076113/C/04/Z; 068545/Z/02 / Wellcome Trust National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Juvenile Diabetes Research Foundation International; Juvenile Diabetes Research Foundation National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) BSIK03009 / Dutch Government National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
Identifiers: 9935266208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article