Gene-level association analysis of systemic sclerosis

Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations w...

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Detalles Bibliográficos
Autores: Gorlova, Olga Y., Li, Yafang, Gorlov, Ivan, Ying, Jun, Chen, Wei V., Assassi, Shervin|||0000-0002-8059-9978, Reveille, John D., Arnett, Frank C., Zhou, Xiaodong, Bossini-Castillo, Lara|||0000-0002-5471-5824, Lopez-Isac, Elena, Acosta-Herrera, Marialbert|||0000-0002-9868-6535, Gregersen, Peter K.|||0000-0003-1613-1518, Lee, Annette T., Steen, Virginia D., Fessler, Barri J., Khanna, Dinesh, Schiopu, Elena, Silver, Richard M., Molitor, Jerry A., Furst, Daniel E., Kafaja, Suzanne, Simms, Robert W., Lafyatis, Robert A., Carreira, Patricia E.|||0000-0001-8279-3806, Simeón-Aznar, Carmen Pilar|||0000-0003-3390-9029, Castellvi, Ivan|||0000-0002-5410-5807, Beltran Catalan, Emma|||0000-0001-8070-6916, Ortego-Centeno, Norberto|||0000-0003-2325-0937, Amos, Christopher I., Martín, Javier|||0000-0002-2202-0622, Mayes, Maureen D.|||0000-0001-5070-2535
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:287385
Acceso en línea:https://ddd.uab.cat/record/287385
https://dx.doi.org/urn:doi:10.1371/journal.pone.0189498
Access Level:acceso abierto
Palabra clave:African Continental Ancestry Group
European Continental Ancestry Group
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Scleroderma, Systemic
Descripción
Sumario:Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly due to the limited sample size of African Americans.

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