Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels.
Overexpression of the cytokine BAFF and autoimmunity risk / Steri, M.; Orru, V.; Idda, M. L.; Pitzalis, M.; Pala, M.; Zara, I.; Sidore, C.; Faa, V.; Floris, M.; Deiana, M.; Asunis, I.; Porcu, E.; Mulas, A.; Piras, M. G.; Lobina, M.; Lai, S.; Marongiu, M.; Serra, V.; Marongiu, M.; Sole, G.; Busonero, F.; Maschio, A.; Cusano, R.; Cuccuru, G.; Deidda, F.; Poddie, F.; Farina, G.; Dei, Marcello; Virdis, F.; Olla, S.; Satta, M. A.; Pani, M.; Delitala, A.; Cocco, Emilio; Frau, J.; Coghe, G.; Lorefice, L.; Fenu, G.; Ferrigno, P.; Ban, M.; Barizzone, N.; Leone, M.; Guerini, F. R.; Piga, M.; Firinu, D.; Kockum, I.; Bomfim, I. Lima; Olsson, T.; Alfredsson, L.; Suarez, A.; Carreira, P. E.; Castillo-Palma, M. J.; Marcus, J. H.; Congia, M.; Angius, A.; Melis, M.; Gonzalez, A.; Riquelme, M. E. A.; Da Silva, B. M.; Marchini, Michele; Danieli, M. G.; Del Giacco, Stefano R; Mathieu, A.; Pani, A.; Montgomery, S. B.; Rosati, Gianmarco; Hillert, J.; Sawcer, S.; D'Falfonso, S.; Todd, J. A.; Novembre, J.; Abecasis, G. R.; Whalen, M. B.; Marrosu, M. G.; Meloni, A.; SANNA RICUPERO, Silvia; Gorospe, M.; Schlessinger, D.; Fiorillo, E.; Zoledziewska, M.; Cucca, F.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - STAMPA. - 376:17(2017), pp. 1615-1626. [10.1056/NEJMoa1610528]
Overexpression of the cytokine BAFF and autoimmunity risk
DEI, MARCELLOMembro del Collaboration Group
;COCCO, EMILIOMembro del Collaboration Group
;Melis, M.Membro del Collaboration Group
;Marchini, MicheleMembro del Collaboration Group
;Danieli, M. G.Membro del Collaboration Group
;ROSATI, GIANMARCOMembro del Collaboration Group
;SANNA RICUPERO, SILVIAMembro del Collaboration Group
;
2017-01-01
Abstract
Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
