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GWAS Study

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

Trynka G, Hunt KA, Bockett NA et al.

22057235 PubMed ID
GWAS Study Type
24269 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

TG
Trynka G
HK
Hunt KA
BN
Bockett NA
RJ
Romanos J
MV
Mistry V
SA
Szperl A
BS
Bakker SF
BM
Bardella MT
BL
Bhaw-Rosun L
CG
Castillejo G
DL
de la Concha EG
DA
de Almeida RC
DK
Dias KR
VD
van Diemen CC
DP
Dubois PC
DR
Duerr RH
ES
Edkins S
FL
Franke L
FK
Fransen K
GJ
Gutierrez J
HG
Heap GA
HB
Hrdlickova B
HS
Hunt S
PI
Plaza Izurieta L
IV
Izzo V
JL
Joosten LA
LC
Langford C
MM
Mazzilli MC
MC
Mein CA
MV
Midah V
MM
Mitrovic M
MB
Mora B
MM
Morelli M
NS
Nutland S
NC
Núñez C
OS
Onengut-Gumuscu S
PK
Pearce K
PM
Platteel M
PI
Polanco I
PS
Potter S
RC
Ribes-Koninckx C
RI
Ricaño-Ponce I
RS
Rich SS
RA
Rybak A
SJ
Santiago JL
SS
Senapati S
SA
Sood A
SH
Szajewska H
TR
Troncone R
VJ
Varadé J
WC
Wallace C
WV
Wolters VM
ZA
Zhernakova A
TB
Thelma BK
CB
Cukrowska B
UE
Urcelay E
BJ
Bilbao JR
MM
Mearin ML
BD
Barisani D
BJ
Barrett JC
PV
Plagnol V
DP
Deloukas P
WC
Wijmenga C
VH
van Heel DA
Chapter II

Abstract

Summary of the research findings

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.

11,812 European ancestry cases, 229 Indian ancestry cases, 11,837 European ancestry controls, 391 Indian ancestry controls

Chapter III

Study Statistics

Key metrics and study information

24269
Total Participants
GWAS
Study Type
No
Replicated
European, South Asian
Ancestry
Netherlands, Poland, U.K., Italy, Spain, India
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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