2026-04-14T02:53:45Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4726892025-07-29T22:28:07Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Gorlova, Olga Y. author Li, Yafang author Gorlov, Ivan author Ying, Jun author Chen, Wei V. author Assassi, Shervin author Reveille, John D. author Arnett, Frank C. author Zhou, Xiaodong author Bossini-Castillo, Lara author Lopez-Isac, Elena author Acosta-Herrera, Marialbert author Gregersen, Peter K. author Lee, Annette T. author Steen, Virginia D. author Fessler, Barri J. author Khanna, Dinesh author Schiopu, Elena author Silver, Richard M. author Molitor, Jerry A. author Furst, Daniel E. author Kafaja, Suzanne author Simms, Robert W. author Lafyatis, Robert A. author Carreira, Patricia E author Simeón-Aznar, Carmen Pilar author Castellvi, Ivan author Beltran Catalan, Emma author Ortego, Norberto author Amos, Christopher I. author Martin, Javier author Mayes, Maureen D. author Universitat Autònoma de Barcelona author 2018 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. African Continental Ancestry Group European Continental Ancestry Group Genome-Wide Association Study Humans Polymorphism, Single Nucleotide Scleroderma, Systemic Gene-level association analysis of systemic sclerosis : A comparison of African-Americans and White populations