Lopez-Isac, Elena ORCID: 0000-0001-8806-5148, Acosta-Herrera, Marialbert, Kerick, Martin, Assassi, Shervin, Satpathy, Ansuman T., Granja, Jeffrey, Mumbach, Maxwell R., Beretta, Lorenzo, Simeon, Carmen P., Carreira, Patricia, Ortego-Centeno, Norberto ORCID: 0000-0003-2325-0937, Castellvi, Ivan ORCID: 0000-0002-5410-5807, Bossini-Castillo, Lara ORCID: 0000-0002-5471-5824, David Carmona, F., Orozco, Gisela ORCID: 0000-0002-3479-0448, Hunzelmann, Nicolas, Distler, Joerg H. W., Franke, Andre, Lunardi, Claudio, Moroncini, Gianluca, Gabrielli, Armando, de Vries-Bouwstra, Jeska, Wijmenga, Cisca ORCID: 0000-0002-5635-1614, Koeleman, Bobby P. C., Nordin, Annika, Padyukov, Leonid, Hoffmann-Vold, Anna-Maria, Lie, Benedicte, Rios, R., Callejas, J. L., Vargas-Hitos, J. A., Garcia-Portales, R., Camps, M. T., Fernandez-Nebro, A., Gonzalez-Escribano, M. F., Garcia-Hernandez, F. J., Castillo, M. J., Aguirre, M. A., Gomez-Gracia, I., Fernandez-Gutierrez, B., Rodriguez-Rodriguez, L., Garcia de la Pena, P., Vicente, E., Andreu, J. L., Fernandez de Castro, M., Lopez-Longo, F. J., Martinez, L., Fonollosa, V, Guillen, A., Espinosa, G., Tolosa, C., Pros, A., Rodriguez-Carballeira, M., Narvaez, F. J., Rubio-Rivas, M., Ortiz-Santamaria, V, Madronero, A. B., Gonzalez-Gay, M. A., Diaz, B., Trapiella, L., Sousa, A., Egurbide, M. V., Fanlo-Mateo, P., Saez-Comet, L., Diaz, F., Hernandez, V, Beltran, E., Roman-Ivorra, J. A., Grau, E., Alegre-Sancho, J. J., Freire, M., Blanco-Garcia, F. J., Oreiro, N., Witte, T., Kreuter, A., Riemekasten, G., Airo, P., Magro, C., Voskuyl, A. E., Vonk, M. C., Hesselstrand, R., Proudman, Susanna, Stevens, Wendy, Nikpour, Mandana, Zochling, J., Sahhar, J., Roddy, J., Nash, P., Tymms, K., Rischmueller, M., Lester, S., Vyse, Timothy, Herrick, Ariane L., Worthington, Jane, Denton, Christopher P., Allanore, Yannick, Brown, Matthew A., Radstake, Timothy R. D. J., Fonseca, Carmen, Chang, Howard Y., Mayes, Maureen D. and Martin, Javier ORCID: 0000-0002-2202-0622 (2019). GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

Full text not available from this repository.

Abstract

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lopez-Isac, ElenaUNSPECIFIEDorcid.org/0000-0001-8806-5148UNSPECIFIED
Acosta-Herrera, MarialbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerick, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assassi, ShervinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Satpathy, Ansuman T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Granja, JeffreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mumbach, Maxwell R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beretta, LorenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simeon, Carmen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carreira, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortego-Centeno, NorbertoUNSPECIFIEDorcid.org/0000-0003-2325-0937UNSPECIFIED
Castellvi, IvanUNSPECIFIEDorcid.org/0000-0002-5410-5807UNSPECIFIED
Bossini-Castillo, LaraUNSPECIFIEDorcid.org/0000-0002-5471-5824UNSPECIFIED
David Carmona, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orozco, GiselaUNSPECIFIEDorcid.org/0000-0002-3479-0448UNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Distler, Joerg H. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lunardi, ClaudioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moroncini, GianlucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabrielli, ArmandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries-Bouwstra, JeskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wijmenga, CiscaUNSPECIFIEDorcid.org/0000-0002-5635-1614UNSPECIFIED
Koeleman, Bobby P. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordin, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Padyukov, LeonidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann-Vold, Anna-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lie, BenedicteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rios, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Callejas, J. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vargas-Hitos, J. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Portales, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Camps, M. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Nebro, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Escribano, M. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Hernandez, F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castillo, M. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aguirre, M. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomez-Gracia, I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Gutierrez, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Rodriguez, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia de la Pena, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vicente, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andreu, J. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez de Castro, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Longo, F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonollosa, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guillen, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espinosa, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tolosa, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pros, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Carballeira, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Narvaez, F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubio-Rivas, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz-Santamaria, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madronero, A. B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Gay, M. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diaz, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trapiella, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sousa, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egurbide, M. V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fanlo-Mateo, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saez-Comet, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diaz, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beltran, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roman-Ivorra, J. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grau, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alegre-Sancho, J. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freire, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanco-Garcia, F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oreiro, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witte, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuter, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemekasten, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Airo, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Magro, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voskuyl, A. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vonk, M. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hesselstrand, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Proudman, SusannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stevens, WendyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikpour, MandanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zochling, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahhar, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roddy, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nash, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tymms, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rischmueller, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lester, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vyse, TimothyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrick, Ariane L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worthington, JaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denton, Christopher P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allanore, YannickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brown, Matthew A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radstake, Timothy R. D. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonseca, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang, Howard Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayes, Maureen D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, JavierUNSPECIFIEDorcid.org/0000-0002-2202-0622UNSPECIFIED
URN: urn:nbn:de:hbz:38-130088
DOI: 10.1038/s41467-019-12760-y
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; HUMAN-CELLS; VARIANTS; REVEALS; ANNOTATION; GENES; CLASSIFICATION; VISUALIZATION; AUTOIMMUNITY; METAANALYSISMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13008

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