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; Róza Ádány; Arpo Aromaa; Maria Teresa Bardella; Leonard H. Van Den Berg; Nicholas A. Bockett; Emilio G. De La Concha; Bárbara Dema; Rudolf S.N. Fehrmann; Miguel Fernández-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 Mäki; Maria Cristina Mazzilli; Owen T. McCann; M. Luisa Mearin; Charles A. Mein; Muddassar M. Mirza; Vanisha Mistry; Barbara Mora; Katherine I. Morley; Chris J. Mulder; Joseph A. Murray; Concepción Ñez; 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, Róza Ádány, Arpo Aromaa, Maria Teresa Bardella, Leonard H. Van Den Berg, Nicholas A. Bockett, Emilio G. De La Concha, Bárbara Dema, Rudolf S.N. Fehrmann, Miguel Fernández-Arquero, Szilvia Fiatal, Elvira Grandone, Peter M. GreenHarry J.M. Groen, Rhian Gwilliam, Roderick H.J. Houwen, Sarah E. Hunt, Katri Kaukinen, Dermot Kelleher, Ilma Korponay-Szabo, Kalle Kurppa, Padraic MacMathuna, Markku Mäki, Maria Cristina Mazzilli, Owen T. McCann, M. Luisa Mearin, Charles A. Mein, Muddassar M. Mirza, Vanisha Mistry, Barbara Mora, Katherine I. Morley, Chris J. Mulder, Joseph A. Murray, Concepción Ñez, 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

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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 × 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)	295-302
Number of pages	8
Journal	Nature Genetics
Volume	42
Issue number	4
DOIs	https://doi.org/10.1038/ng.543
Publication status	Published - 1 Apr 2010

Keywords

Econometric and Statistical Methods: General
Geneeskunde (GENK)
Geneeskunde(GENK)
Medical sciences
Bescherming en bevordering van de menselijke gezondheid

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Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G. A. R., Ádány, 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., Fernández-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), 295-302. https://doi.org/10.1038/ng.543

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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 PGWAS<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 × 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.",

keywords = "Econometric and Statistical Methods: General, Geneeskunde (GENK), Geneeskunde(GENK), Medical sciences, Bescherming en bevordering van de menselijke gezondheid",

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 R{\'o}za {\'A}d{\'a}ny and Arpo Aromaa and Bardella, {Maria Teresa} and {Van Den Berg}, {Leonard H.} and Bockett, {Nicholas A.} and {De La Concha}, {Emilio G.} and B{\'a}rbara Dema and Fehrmann, {Rudolf S.N.} and Miguel Fern{\'a}ndez-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 M{\"a}ki 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 Morley, {Katherine I.} and Mulder, {Chris J.} and Murray, {Joseph A.} and Concepci{\'o}n {\~N}ez 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.}",

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volume = "42",

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Dubois, PCA, Trynka, G, Franke, L, Hunt, KA, Romanos, J, Curtotti, A, Zhernakova, A, Heap, GAR, Ádány, R, Aromaa, A, Bardella, MT, Van Den Berg, LH, Bockett, NA, De La Concha, EG, Dema, B, Fehrmann, RSN, Fernández-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, Mäki, M, Mazzilli, MC, McCann, OT, Mearin, ML, Mein, CA, Mirza, MM, Mistry, V, Mora, B, Morley, KI, Mulder, CJ, Murray, JA, Ñez, 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. 295-302. 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 - Ádány, Róza

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, Bárbara

AU - Fehrmann, Rudolf S.N.

AU - Fernández-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 - Mäki, 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 I.

AU - Mulder, Chris J.

AU - Murray, Joseph A.

AU - Ñez, Concepción

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 - 2010/4/1

Y1 - 2010/4/1

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 PGWAS<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 × 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 PGWAS<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 × 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.

KW - Econometric and Statistical Methods: General

KW - Geneeskunde (GENK)

KW - Geneeskunde(GENK)

KW - Medical sciences

KW - Bescherming en bevordering van de menselijke gezondheid

UR - http://www.scopus.com/inward/record.url?scp=77950243833&partnerID=8YFLogxK

U2 - 10.1038/ng.543

DO - 10.1038/ng.543

M3 - Article

C2 - 20190752

SN - 1061-4036

VL - 42

SP - 295

EP - 302

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Multiple common variants for celiac disease influencing immune gene expression

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