Multiple common variants for celiac disease influencing immune gene expression

Patrick C. A. Dubois; Gosia Trynka; Lude Franke; Karen A. Hunt; Jihane Romanos; Alessandra Curtotti; Alexandra Zhernakova; Graham A. R. Heap; Roza Adany; Arpo Aromaa; Maria Teresa Bardella; Leonard H. van den Berg; Nicholas A. Bockett; Emilio G. de la Concha; Barbara Dema; Rudolf S. N. Fehrmann; Miguel Fernandez-Arquero; Szilvia Fiatal; Elvira Grandone; Peter M. Green; Harry J. M. Groen; Rhian Gwilliam; Roderick H. J. Houwen; Sarah E. Hunt; Katri Kaukinen; Dermot Kelleher; Ilma Korponay-Szabo; Kalle Kurppa; Padraic MacMathuna; Markku Maki; Maria Cristina Mazzilli; Owen T. McCann; M. Luisa Mearin; Charles A. Mein; Muddassar M. Mirza; Vanisha Mistry; Barbara Mora; Katherine Morley; Chris J. Mulder; Joseph A. Murray; Concepcion Nunez; Elvira Oosterom; Roel A. Ophoff; Isabel Polanco; Leena Peltonen; Mathieu Platteel; Anna Rybak; Veikko Salomaa; Joachim J. Schweizer; Maria Pia Sperandeo; Greetje J. Tack; Graham Turner; Jan H. Veldink; Wieke H. M. Verbeek; Rinse K. Weersma; Victorien M. Wolters; Elena Urcelay; Bozena Cukrowska; Luigi Greco; Susan L. Neuhausen; Ross McManus; Donatella Barisani; Panos Deloukas; Jeffrey C. Barrett; Paivi Saavalainen; Cisca Wijmenga; David A. van Heel

doi:10.1038/ng.543

Multiple common variants for celiac disease influencing immune gene expression

Patrick C. A. Dubois
, Gosia Trynka
, Lude Franke
, Karen A. Hunt
, Jihane Romanos
, Alessandra Curtotti
, Alexandra Zhernakova
, Graham A. R. Heap
, Roza Adany
, Arpo Aromaa
, Maria Teresa Bardella
, Leonard H. van den Berg
, Nicholas A. Bockett
, Emilio G. de la Concha
, Barbara Dema
, Rudolf S. N. Fehrmann
, Miguel Fernandez-Arquero
, Szilvia Fiatal
, Elvira Grandone
, Peter M. Green

Harry J. M. Groen, Rhian Gwilliam, Roderick H. J. Houwen, Sarah E. Hunt, Katri Kaukinen, Dermot Kelleher, Ilma Korponay-Szabo, Kalle Kurppa, Padraic MacMathuna, Markku Maki, Maria Cristina Mazzilli, Owen T. McCann, M. Luisa Mearin, Charles A. Mein, Muddassar M. Mirza, Vanisha Mistry, Barbara Mora, Katherine Morley, Chris J. Mulder, Joseph A. Murray, Concepcion Nunez, Elvira Oosterom, Roel A. Ophoff, Isabel Polanco, Leena Peltonen, Mathieu Platteel, Anna Rybak, Veikko Salomaa, Joachim J. Schweizer, Maria Pia Sperandeo, Greetje J. Tack, Graham Turner, Jan H. Veldink, Wieke H. M. Verbeek, Rinse K. Weersma, Victorien M. Wolters, Elena Urcelay, Bozena Cukrowska, Luigi Greco, Susan L. Neuhausen, Ross McManus, Donatella Barisani, Panos Deloukas, Jeffrey C. Barrett, Paivi Saavalainen, Cisca Wijmenga, David A. van Heel

Queen Mary University of London
Univ Med Ctr Groningen
UMC University Medical Center Utrecht
University of Debrecen
Natl Inst Hlth & Welf, Helsinki
Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn IRCCS
University of Milan
Hosp Clin San Carlos, Dept Clin Immunol
Wellcome Sanger Institute
University of Tampere
Tampere University Hospital
Trinity College Dublin
Heim Pal Childrens Hosp, Budapest
Mater Misericordiae University Hospital
Sapienza University of Rome
LUMC Leiden University Medical Center
Kings Coll London, Guys Hosp
VU Amsterdam
Mayo Clinic
University of California, Los Angeles
Hosp La Paz, Dept Pediat Gastroenterol
FIMM, Helsinki
Childrens Mem Hlth Inst, Dept Gastroenterol Hepatol & Immunol
University of Naples Federico II
University of Groningen
Childrens Mem Hlth Inst, Dept Pathol
City of Hope
Università degli Studi di Milano-Bicocca
University of Helsinki

Research output: Contribution to journal › Article › peer-review

891 Citations (Scopus)

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.

Original language	English
Pages (from-to)	295 - U42
Number of pages	8
Journal	Nature Genetics
Volume	42
Issue number	4
DOIs	https://doi.org/10.1038/ng.543
Publication status	Published - Apr 2010

Access to Document

10.1038/ng.543

Cite this

Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G. A. R., Adany, R., Aromaa, A., Bardella, M. T., van den Berg, L. H., Bockett, N. A., de la Concha, E. G., Dema, B., Fehrmann, R. S. N., Fernandez-Arquero, M., Fiatal, S., Grandone, E., ... van Heel, D. A. (2010). Multiple common variants for celiac disease influencing immune gene expression. Nature Genetics, 42(4), 295 - U42. https://doi.org/10.1038/ng.543

@article{fa33b1f0df7b47c9b0f2b3358f39a72c,

title = "Multiple common variants for celiac disease influencing immune gene expression",

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.",

author = "Dubois, \{Patrick C. A.\} and Gosia Trynka and Lude Franke and Hunt, \{Karen A.\} and Jihane Romanos and Alessandra Curtotti and Alexandra Zhernakova and Heap, \{Graham A. R.\} and Roza Adany and Arpo Aromaa and Bardella, \{Maria Teresa\} and \{van den Berg\}, \{Leonard H.\} and Bockett, \{Nicholas A.\} and \{de la Concha\}, \{Emilio G.\} and Barbara Dema and Fehrmann, \{Rudolf S. N.\} and Miguel Fernandez-Arquero and Szilvia Fiatal and Elvira Grandone and Green, \{Peter M.\} and Groen, \{Harry J. M.\} and Rhian Gwilliam and Houwen, \{Roderick H. J.\} and Hunt, \{Sarah E.\} and Katri Kaukinen and Dermot Kelleher and Ilma Korponay-Szabo and Kalle Kurppa and Padraic MacMathuna and Markku Maki and Mazzilli, \{Maria Cristina\} and McCann, \{Owen T.\} and Mearin, \{M. Luisa\} and Mein, \{Charles A.\} and Mirza, \{Muddassar M.\} and Vanisha Mistry and Barbara Mora and Katherine Morley and Mulder, \{Chris J.\} and Murray, \{Joseph A.\} and Concepcion Nunez and Elvira Oosterom and Ophoff, \{Roel A.\} and Isabel Polanco and Leena Peltonen and Mathieu Platteel and Anna Rybak and Veikko Salomaa and Schweizer, \{Joachim J.\} and Sperandeo, \{Maria Pia\} and Tack, \{Greetje J.\} and Graham Turner and Veldink, \{Jan H.\} and Verbeek, \{Wieke H. M.\} and Weersma, \{Rinse K.\} and Wolters, \{Victorien M.\} and Elena Urcelay and Bozena Cukrowska and Luigi Greco and Neuhausen, \{Susan L.\} and Ross McManus and Donatella Barisani and Panos Deloukas and Barrett, \{Jeffrey C.\} and Paivi Saavalainen and Cisca Wijmenga and \{van Heel\}, \{David A.\}",

year = "2010",

month = apr,

doi = "10.1038/ng.543",

language = "English",

volume = "42",

pages = "295 -- U42",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Research",

number = "4",

}

Dubois, PCA, Trynka, G, Franke, L, Hunt, KA, Romanos, J, Curtotti, A, Zhernakova, A, Heap, GAR, Adany, R, Aromaa, A, Bardella, MT, van den Berg, LH, Bockett, NA, de la Concha, EG, Dema, B, Fehrmann, RSN, Fernandez-Arquero, M, Fiatal, S, Grandone, E, Green, PM, Groen, HJM, Gwilliam, R, Houwen, RHJ, Hunt, SE, Kaukinen, K, Kelleher, D, Korponay-Szabo, I, Kurppa, K, MacMathuna, P, Maki, M, Mazzilli, MC, McCann, OT, Mearin, ML, Mein, CA, Mirza, MM, Mistry, V, Mora, B, Morley, K, Mulder, CJ, Murray, JA, Nunez, 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, WHM, 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 2010, 'Multiple common variants for celiac disease influencing immune gene expression', Nature Genetics, vol. 42, no. 4, pp. 295 - U42. https://doi.org/10.1038/ng.543

TY - JOUR

T1 - Multiple common variants for celiac disease influencing immune gene expression

AU - Dubois, Patrick C. A.

AU - Trynka, Gosia

AU - Franke, Lude

AU - Hunt, Karen A.

AU - Romanos, Jihane

AU - Curtotti, Alessandra

AU - Zhernakova, Alexandra

AU - Heap, Graham A. R.

AU - Adany, Roza

AU - Aromaa, Arpo

AU - Bardella, Maria Teresa

AU - van den Berg, Leonard H.

AU - Bockett, Nicholas A.

AU - de la Concha, Emilio G.

AU - Dema, Barbara

AU - Fehrmann, Rudolf S. N.

AU - Fernandez-Arquero, Miguel

AU - Fiatal, Szilvia

AU - Grandone, Elvira

AU - Green, Peter M.

AU - Groen, Harry J. M.

AU - Gwilliam, Rhian

AU - Houwen, Roderick H. J.

AU - Hunt, Sarah E.

AU - Kaukinen, Katri

AU - Kelleher, Dermot

AU - Korponay-Szabo, Ilma

AU - Kurppa, Kalle

AU - MacMathuna, Padraic

AU - Maki, Markku

AU - Mazzilli, Maria Cristina

AU - McCann, Owen T.

AU - Mearin, M. Luisa

AU - Mein, Charles A.

AU - Mirza, Muddassar M.

AU - Mistry, Vanisha

AU - Mora, Barbara

AU - Morley, Katherine

AU - Mulder, Chris J.

AU - Murray, Joseph A.

AU - Nunez, Concepcion

AU - Oosterom, Elvira

AU - Ophoff, Roel A.

AU - Polanco, Isabel

AU - Peltonen, Leena

AU - Platteel, Mathieu

AU - Rybak, Anna

AU - Salomaa, Veikko

AU - Schweizer, Joachim J.

AU - Sperandeo, Maria Pia

AU - Tack, Greetje J.

AU - Turner, Graham

AU - Veldink, Jan H.

AU - Verbeek, Wieke H. M.

AU - Weersma, Rinse K.

AU - Wolters, Victorien M.

AU - Urcelay, Elena

AU - Cukrowska, Bozena

AU - Greco, Luigi

AU - Neuhausen, Susan L.

AU - McManus, Ross

AU - Barisani, Donatella

AU - Deloukas, Panos

AU - Barrett, Jeffrey C.

AU - Saavalainen, Paivi

AU - Wijmenga, Cisca

AU - van Heel, David A.

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

U2 - 10.1038/ng.543

DO - 10.1038/ng.543

M3 - Article

SN - 1546-1718

VL - 42

SP - 295 - U42

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Multiple common variants for celiac disease influencing immune gene expression

Abstract

Access to Document

Fingerprint

Cite this