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., et al.. - 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.
