title: Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease.
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.
authors: Genetics Department, University Medical Center and University of Groningen, The Netherlands.
authors: Gosia
authors: G
authors: Trynka
authors: Karen A
authors: KA
authors: Hunt
authors: Nicholas A
authors: NA
authors: Bockett
authors: Jihane
authors: J
authors: Romanos
authors: Vanisha
authors: V
authors: Mistry
authors: Agata
authors: A
authors: Szperl
authors: Sjoerd F
authors: SF
authors: Bakker
authors: Maria Teresa
authors: MT
authors: Bardella
authors: Leena
authors: L
authors: Bhaw-Rosun
authors: Gemma
authors: G
authors: Castillejo
authors: Emilio G
authors: EG
authors: de la Concha
authors: Rodrigo Coutinho
authors: RC
authors: de Almeida
authors: Kerith-Rae M
authors: KR
authors: Dias
authors: Cleo C
authors: CC
authors: van Diemen
authors: Patrick C A
authors: PC
authors: Dubois
authors: Richard H
authors: RH
authors: Duerr
authors: Sarah
authors: S
authors: Edkins
authors: Lude
authors: L
authors: Franke
authors: Karin
authors: K
authors: Fransen
authors: Javier
authors: J
authors: Gutierrez
authors: Graham A R
authors: GA
authors: Heap
authors: Barbara
authors: B
authors: Hrdlickova
authors: Sarah
authors: S
authors: Hunt
authors: Leticia
authors: L
authors: Plaza Izurieta
authors: Valentina
authors: V
authors: Izzo
authors: Leo A B
authors: LA
authors: Joosten
authors: Cordelia
authors: C
authors: Langford
authors: Maria Cristina
authors: MC
authors: Mazzilli
authors: Charles A
authors: CA
authors: Mein
authors: Vandana
authors: V
authors: Midah
authors: Mitja
authors: M
authors: Mitrovic
authors: Barbara
authors: B
authors: Mora
authors: Marinita
authors: M
authors: Morelli
authors: Sarah
authors: S
authors: Nutland
authors: Concepción
authors: C
authors: Núñez
authors: Suna
authors: S
authors: Onengut-Gumuscu
authors: Kerra
authors: K
authors: Pearce
authors: Mathieu
authors: M
authors: Platteel
authors: Isabel
authors: I
authors: Polanco
authors: Simon
authors: S
authors: Potter
authors: Carmen
authors: C
authors: Ribes-Koninckx
authors: Isis
authors: I
authors: Ricaño-Ponce
authors: Stephen S
authors: SS
authors: Rich
authors: Anna
authors: A
authors: Rybak
authors: José Luis
authors: JL
authors: Santiago
authors: Sabyasachi
authors: S
authors: Senapati
authors: Ajit
authors: A
authors: Sood
authors: Hania
authors: H
authors: Szajewska
authors: Riccardo
authors: R
authors: Troncone
authors: Jezabel
authors: J
authors: Varadé
authors: Chris
authors: C
authors: Wallace
authors: Victorien M
authors: VM
authors: Wolters
authors: Alexandra
authors: A
authors: Zhernakova
authors: B K
authors: BK
authors: Thelma
authors: Bozena
authors: B
authors: Cukrowska
authors: Elena
authors: E
authors: Urcelay
authors: Jose Ramon
authors: JR
authors: Bilbao
authors: M Luisa
authors: ML
authors: Mearin
authors: Donatella
authors: D
authors: Barisani
authors: Jeffrey C
authors: JC
authors: Barrett
authors: Vincent
authors: V
authors: Plagnol
authors: Panos
authors: P
authors: Deloukas
authors: Cisca
authors: C
authors: Wijmenga
authors: David A
authors: DA
authors: van Heel
mesh_terms: D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D002874:Chromosome Mapping; D005787:Gene Frequency; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors