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PMID: 20190752 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Multiple common variants for celiac disease influencing immune gene expression.

Nature genetics ·Vol. 42 ·No. 4 ·2010-04-00 ·Pages 295-302

Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GA, Adány R, Aromaa A, Bardella MT, van den Berg LH, Bockett NA, de la Concha EG, Dema B, Fehrmann RS, Fernández-Arquero M, Fiatal S, Grandone E, Green PM, Groen HJ, Gwilliam R, Houwen RH, Hunt SE, Kaukinen K, Kelleher D, Korponay-Szabo I, Kurppa K, MacMathuna P, Mäki M, Mazzilli MC, McCann OT, Mearin ML, Mein CA, Mirza MM, Mistry V, Mora B, Morley KI, Mulder CJ, Murray JA, Núñez C, Oosterom E, Ophoff RA, Polanco I, Peltonen L, Platteel M, Rybak A, Salomaa V, Schweizer JJ, Sperandeo MP, Tack GJ, Turner G, Veldink JH, Verbeek WH, Weersma RK, Wolters VM, Urcelay E, Cukrowska B, Greco L, Neuhausen SL, McManus R, Barisani D, Deloukas P, Barrett JC, Saavalainen P, Wijmenga C, van Heel DA

Abstract

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.

MeSH Terms
Case-Control Studies Celiac Disease/genetics Gene Expression Gene Expression Profiling Genes, MHC Class I Genome-Wide Association Study Humans Meta-Analysis as Topic Polymorphism, Single Nucleotide Risk
Authors & Affiliations
67 authors, click to expand affiliations / ORCID
Dubois Patrick C A
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
Franke Lude
Hunt Karen A
Romanos Jihane
Curtotti Alessandra
Zhernakova Alexandra
Heap Graham A R
Adány Róza
Aromaa Arpo
Bardella Maria Teresa
van den Berg Leonard H
Bockett Nicholas A
de la Concha Emilio G
Dema Bárbara
Fehrmann Rudolf S N
Fernández-Arquero Miguel
Fiatal Szilvia
Grandone Elvira
Green Peter M
Groen Harry J M
Gwilliam Rhian
Houwen Roderick H J
Hunt Sarah E
Kaukinen Katri
Kelleher Dermot
Korponay-Szabo Ilma
Kurppa Kalle
MacMathuna Padraic
Mäki Markku
Mazzilli Maria Cristina
McCann Owen T
Mearin M Luisa
Mein Charles A
Mirza Muddassar M
Mistry Vanisha
Mora Barbara
Morley Katherine I
Mulder Chris J
Murray Joseph A
Núñez Concepción
Oosterom Elvira
Ophoff Roel A
Polanco Isabel
Peltonen Leena
Platteel Mathieu
Rybak Anna
Salomaa Veikko
Schweizer Joachim J
Sperandeo Maria Pia
Tack Greetje J
Turner Graham
Veldink Jan H
Verbeek Wieke H M
Weersma Rinse K
Wolters Victorien M
Urcelay Elena
Cukrowska Bozena
Greco Luigi
Neuhausen Susan L
McManus Ross
Barisani Donatella
Deloukas Panos
Barrett Jeffrey C
Saavalainen Paivi
Wijmenga Cisca
van Heel David A
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.543
Published
2010-04-00
Epub
2010-00-28
Pages
295-302
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2847618
Subset
IM
Grants
NIDDK NIH HHS · R01 DK071003 · United States
NIDDK NIH HHS · DK081645 · United States
NIDDK NIH HHS · DK57892 · United States
NIDDK NIH HHS · R01 DK081645 · United States
NIDDK NIH HHS · R56 DK071003 · United States
NIDDK NIH HHS · DK050678 · United States
Medical Research Council · G0700545 · United Kingdom
NIDDK NIH HHS · R01 DK050678 · United States
NIDDK NIH HHS · R01 DK057892 · United States
NINDS NIH HHS · NS058980 · United States
NINDS NIH HHS · R01 NS058980 · United States
NIDDK NIH HHS · U01 DK062418 · United States
Wellcome Trust · 084743 · United Kingdom
Medical Research Council · G0700545(82277) · United Kingdom
NIDDK NIH HHS · DK071003 · United States
Databases
GEO
GSE20142, GSE20332
Corrections
ErratumIn
-
CommentIn
PMID: 20348961
External Links
PubMed source DOI: 10.1038/ng.543 PMC Full Text View journal details
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