Publication

Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations

Coeliac Dis Immunochip Consortium, Rheumatoid Arthrit Consortium Int, Int Scleroderma Grp, Type 1 Diabet Genetics Consortium, Marquez, A., Kerick, M., Zhernakova, A., Gutierrez-Achury, J., Chen, W-M., Onengut-Gumuscu, S., Gonzalez-Alvaro, I., Rodriguez-Rodriguez, L., Rios-Fernandez, R., Gonzalez-Gay, M. A., Mayes, M. D., Raychaudhuri, S., Rich, S. S., Wijmenga, C. & Martin, J., 20-Dec-2018, In : Genome medicine. 10, 1, 13 p., 97.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Coeliac Dis Immunochip Consortium, Rheumatoid Arthrit Consortium Int, Int Scleroderma Grp, Type 1 Diabet Genetics Consortium, Marquez, A., Kerick, M., Zhernakova, A., Gutierrez-Achury, J., Chen, W-M., Onengut-Gumuscu, S., Gonzalez-Alvaro, I., Rodriguez-Rodriguez, L., Rios-Fernandez, R., Gonzalez-Gay, M. A., Mayes, M. D., Raychaudhuri, S., Rich, S. S., Wijmenga, C., & Martin, J. (2018). Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. Genome medicine, 10(1), [97]. https://doi.org/10.1186/s13073-018-0604-8

Author

Coeliac Dis Immunochip Consortium ; Rheumatoid Arthrit Consortium Int ; Int Scleroderma Grp ; Type 1 Diabet Genetics Consortium ; Marquez, Ana ; Kerick, Martin ; Zhernakova, Alexandra ; Gutierrez-Achury, Javier ; Chen, Wei-Min ; Onengut-Gumuscu, Suna ; Gonzalez-Alvaro, Isidoro ; Rodriguez-Rodriguez, Luis ; Rios-Fernandez, Raquel ; Gonzalez-Gay, Miguel A. ; Mayes, Maureen D. ; Raychaudhuri, Soumya ; Rich, Stephen S. ; Wijmenga, Cisca ; Martin, Javier. / Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. In: Genome medicine. 2018 ; Vol. 10, No. 1.

Harvard

Coeliac Dis Immunochip Consortium, Rheumatoid Arthrit Consortium Int, Int Scleroderma Grp, Type 1 Diabet Genetics Consortium, Marquez, A, Kerick, M, Zhernakova, A, Gutierrez-Achury, J, Chen, W-M, Onengut-Gumuscu, S, Gonzalez-Alvaro, I, Rodriguez-Rodriguez, L, Rios-Fernandez, R, Gonzalez-Gay, MA, Mayes, MD, Raychaudhuri, S, Rich, SS, Wijmenga, C & Martin, J 2018, 'Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations', Genome medicine, vol. 10, no. 1, 97. https://doi.org/10.1186/s13073-018-0604-8

Standard

Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. / Coeliac Dis Immunochip Consortium; Rheumatoid Arthrit Consortium Int; Int Scleroderma Grp; Type 1 Diabet Genetics Consortium; Marquez, Ana; Kerick, Martin; Zhernakova, Alexandra; Gutierrez-Achury, Javier; Chen, Wei-Min; Onengut-Gumuscu, Suna; Gonzalez-Alvaro, Isidoro; Rodriguez-Rodriguez, Luis; Rios-Fernandez, Raquel; Gonzalez-Gay, Miguel A.; Mayes, Maureen D.; Raychaudhuri, Soumya; Rich, Stephen S.; Wijmenga, Cisca; Martin, Javier.

In: Genome medicine, Vol. 10, No. 1, 97, 20.12.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Coeliac Dis Immunochip Consortium, Rheumatoid Arthrit Consortium Int, Int Scleroderma Grp, Type 1 Diabet Genetics Consortium, Marquez A, Kerick M et al. Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. Genome medicine. 2018 Dec 20;10(1). 97. https://doi.org/10.1186/s13073-018-0604-8


BibTeX

@article{0ceb043a8022499c9bb7a8928bd9345a,
title = "Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations",
abstract = "BackgroundIn recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component.MethodsFor this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET.ResultsWe identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cell-specific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may act by deregulating gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc, and T1D treatment.ConclusionsIn this study, we have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied.",
keywords = "Celiac disease, Rheumatoid arthritis, Systemic sclerosis, Type 1 diabetes, Cross-disease meta-analysis, Immunochip, Autoimmune disease, functional enrichment analysis, GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, CELIAC-DISEASE, VARIANTS, IMPACT, RISK",
author = "{Coeliac Dis Immunochip Consortium} and {Rheumatoid Arthrit Consortium Int} and {Int Scleroderma Grp} and {Type 1 Diabet Genetics Consortium} and Ana Marquez and Martin Kerick and Alexandra Zhernakova and Javier Gutierrez-Achury and Wei-Min Chen and Suna Onengut-Gumuscu and Isidoro Gonzalez-Alvaro and Luis Rodriguez-Rodriguez and Raquel Rios-Fernandez and Gonzalez-Gay, {Miguel A.} and Mayes, {Maureen D.} and Soumya Raychaudhuri and Rich, {Stephen S.} and Cisca Wijmenga and Javier Martin",
year = "2018",
month = dec,
day = "20",
doi = "10.1186/s13073-018-0604-8",
language = "English",
volume = "10",
journal = "Genome medicine",
issn = "1756-994X",
publisher = "BMC",
number = "1",

}

RIS

TY - JOUR

T1 - Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations

AU - Coeliac Dis Immunochip Consortium

AU - Rheumatoid Arthrit Consortium Int

AU - Int Scleroderma Grp

AU - Type 1 Diabet Genetics Consortium

AU - Marquez, Ana

AU - Kerick, Martin

AU - Zhernakova, Alexandra

AU - Gutierrez-Achury, Javier

AU - Chen, Wei-Min

AU - Onengut-Gumuscu, Suna

AU - Gonzalez-Alvaro, Isidoro

AU - Rodriguez-Rodriguez, Luis

AU - Rios-Fernandez, Raquel

AU - Gonzalez-Gay, Miguel A.

AU - Mayes, Maureen D.

AU - Raychaudhuri, Soumya

AU - Rich, Stephen S.

AU - Wijmenga, Cisca

AU - Martin, Javier

PY - 2018/12/20

Y1 - 2018/12/20

N2 - BackgroundIn recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component.MethodsFor this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET.ResultsWe identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cell-specific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may act by deregulating gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc, and T1D treatment.ConclusionsIn this study, we have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied.

AB - BackgroundIn recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component.MethodsFor this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET.ResultsWe identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cell-specific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may act by deregulating gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc, and T1D treatment.ConclusionsIn this study, we have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied.

KW - Celiac disease

KW - Rheumatoid arthritis

KW - Systemic sclerosis

KW - Type 1 diabetes

KW - Cross-disease meta-analysis

KW - Immunochip

KW - Autoimmune disease

KW - functional enrichment analysis

KW - GENOME-WIDE ASSOCIATION

KW - SUSCEPTIBILITY LOCI

KW - CELIAC-DISEASE

KW - VARIANTS

KW - IMPACT

KW - RISK

U2 - 10.1186/s13073-018-0604-8

DO - 10.1186/s13073-018-0604-8

M3 - Article

C2 - 30572963

VL - 10

JO - Genome medicine

JF - Genome medicine

SN - 1756-994X

IS - 1

M1 - 97

ER -

ID: 74802293