2024-03-28T13:58:12Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1616542022-09-23T06:27:08Zcom_10261_64com_10261_1col_10261_317
DIGITAL.CSIC
author
Gorlova, Olga
author
Li, Yafang
author
Gorlov, Ivan
author
Ying, Jun
author
Chen, Wei V.
author
Assassi, S.
author
Reveille, J. D.
author
Arnett, F. C.
author
Zhou, Xiaodong
author
Bossini-Castillo, L.
author
López-Isac, Elena
author
Acosta-Herrera, Marialbert
author
Gregersen, Peter K.
author
Lee, Annette
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
author
Carreira, P.
author
Simeón, Carmen P.
author
Castellví, I.
author
Beltrán, E.
author
Ortego-Centeno, N.
author
Amos, C. I.
author
Martín, Javier
author
Mayes, Maureen D.
2018-03-05T12:23:01Z
2018-03-05T12:23:01Z
2018-01-02
PLoS ONE
http://hdl.handle.net/10261/161654
1932-6203
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 = 6.13x10-3) 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 = 5.57x10-4) 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.
eng
openAccess
Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
artículo
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URL
https://digital.csic.es/bitstream/10261/161654/1/journal.pone.0189498.pdf
File
MD5
68e2a41e65030123e65bdd59bb3d0e68
610311
application/pdf
journal.pone.0189498.pdf