Multiple common variants for celiac disease influencing immune gene expression.
We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression.
Dubois
Patrick C A
PC
Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Trynka
Gosia
G
Franke
Lude
L
Hunt
Karen A
KA
Romanos
Jihane
J
Curtotti
Alessandra
A
Zhernakova
Alexandra
A
Heap
Graham A R
GA
Adány
Róza
R
Aromaa
Arpo
A
Bardella
Maria Teresa
MT
van den Berg
Leonard H
LH
Bockett
Nicholas A
NA
de la Concha
Emilio G
EG
Dema
Bárbara
B
Fehrmann
Rudolf S N
RS
Fernández-Arquero
Miguel
M
Fiatal
Szilvia
S
Grandone
Elvira
E
Green
Peter M
PM
Groen
Harry J M
HJ
Gwilliam
Rhian
R
Houwen
Roderick H J
RH
Hunt
Sarah E
SE
Kaukinen
Katri
K
Kelleher
Dermot
D
Korponay-Szabo
Ilma
I
Kurppa
Kalle
K
MacMathuna
Padraic
P
Mäki
Markku
M
Mazzilli
Maria Cristina
MC
McCann
Owen T
OT
Mearin
M Luisa
ML
Mein
Charles A
CA
Mirza
Muddassar M
MM
Mistry
Vanisha
V
Mora
Barbara
B
Morley
Katherine I
KI
Mulder
Chris J
CJ
Murray
Joseph A
JA
Núñez
Concepción
C
Oosterom
Elvira
E
Ophoff
Roel A
RA
Polanco
Isabel
I
Peltonen
Leena
L
Platteel
Mathieu
M
Rybak
Anna
A
Salomaa
Veikko
V
Schweizer
Joachim J
JJ
Sperandeo
Maria Pia
MP
Tack
Greetje J
GJ
Turner
Graham
G
Veldink
Jan H
JH
Verbeek
Wieke H M
WH
Weersma
Rinse K
RK
Wolters
Victorien M
VM
Urcelay
Elena
E
Cukrowska
Bozena
B
Greco
Luigi
L
Neuhausen
Susan L
SL
McManus
Ross
R
Barisani
Donatella
D
Deloukas
Panos
P
Barrett
Jeffrey C
JC
Saavalainen
Paivi
P
Wijmenga
Cisca
C
van Heel
David A
DA
D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005805:Genes, MHC Class I; D055106:Genome-Wide Association Study; D006801:Humans; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D012306:Risk