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Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations

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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Autores principales: Gorlova, Olga Y., Li, Yafang, Gorlov, Ivan, Ying, Jun, Chen, Wei V., Assassi, Shervin, Reveille, John D., Arnett, Frank C., Zhou, Xiaodong, Bossini-Castillo, Lara, Lopez-Isac, Elena, Acosta-Herrera, Marialbert, Gregersen, Peter K., 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, Simeon, Carmen Pilar, Castellvi, Ivan, Beltran, Emma, Ortego, Norberto, Amos, Christopher I., Martin, Javier, Mayes, Maureen D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749683/
https://www.ncbi.nlm.nih.gov/pubmed/29293537
http://dx.doi.org/10.1371/journal.pone.0189498
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author Gorlova, Olga Y.
Li, Yafang
Gorlov, Ivan
Ying, Jun
Chen, Wei V.
Assassi, Shervin
Reveille, John D.
Arnett, Frank C.
Zhou, Xiaodong
Bossini-Castillo, Lara
Lopez-Isac, Elena
Acosta-Herrera, Marialbert
Gregersen, Peter K.
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
Simeon, Carmen Pilar
Castellvi, Ivan
Beltran, Emma
Ortego, Norberto
Amos, Christopher I.
Martin, Javier
Mayes, Maureen D.
author_facet Gorlova, Olga Y.
Li, Yafang
Gorlov, Ivan
Ying, Jun
Chen, Wei V.
Assassi, Shervin
Reveille, John D.
Arnett, Frank C.
Zhou, Xiaodong
Bossini-Castillo, Lara
Lopez-Isac, Elena
Acosta-Herrera, Marialbert
Gregersen, Peter K.
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
Simeon, Carmen Pilar
Castellvi, Ivan
Beltran, Emma
Ortego, Norberto
Amos, Christopher I.
Martin, Javier
Mayes, Maureen D.
author_sort Gorlova, Olga Y.
collection PubMed
description 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.
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spelling pubmed-57496832018-01-26 Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations Gorlova, Olga Y. Li, Yafang Gorlov, Ivan Ying, Jun Chen, Wei V. Assassi, Shervin Reveille, John D. Arnett, Frank C. Zhou, Xiaodong Bossini-Castillo, Lara Lopez-Isac, Elena Acosta-Herrera, Marialbert Gregersen, Peter K. 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 Simeon, Carmen Pilar Castellvi, Ivan Beltran, Emma Ortego, Norberto Amos, Christopher I. Martin, Javier Mayes, Maureen D. PLoS One Research Article 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. Public Library of Science 2018-01-02 /pmc/articles/PMC5749683/ /pubmed/29293537 http://dx.doi.org/10.1371/journal.pone.0189498 Text en © 2018 Gorlova et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gorlova, Olga Y.
Li, Yafang
Gorlov, Ivan
Ying, Jun
Chen, Wei V.
Assassi, Shervin
Reveille, John D.
Arnett, Frank C.
Zhou, Xiaodong
Bossini-Castillo, Lara
Lopez-Isac, Elena
Acosta-Herrera, Marialbert
Gregersen, Peter K.
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
Simeon, Carmen Pilar
Castellvi, Ivan
Beltran, Emma
Ortego, Norberto
Amos, Christopher I.
Martin, Javier
Mayes, Maureen D.
Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
title Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
title_full Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
title_fullStr Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
title_full_unstemmed Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
title_short Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
title_sort gene-level association analysis of systemic sclerosis: a comparison of african-americans and white populations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749683/
https://www.ncbi.nlm.nih.gov/pubmed/29293537
http://dx.doi.org/10.1371/journal.pone.0189498
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