Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783289613898481664 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5749683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gorlovaolgay genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT liyafang genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT gorlovivan genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT yingjun genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT chenweiv genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT assassishervin genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT reveillejohnd genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT arnettfrankc genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT zhouxiaodong genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT bossinicastillolara genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT lopezisacelena genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT acostaherreramarialbert genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT gregersenpeterk genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT leeannettet genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT steenvirginiad genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT fesslerbarrij genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT khannadinesh genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT schiopuelena genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT silverrichardm genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT molitorjerrya genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT furstdaniele genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT kafajasuzanne genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT simmsrobertw genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT lafyatisroberta genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT carreirapatricia genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT simeoncarmenpilar genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT castellviivan genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT beltranemma genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT ortegonorberto genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT amoschristopheri genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT martinjavier genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations AT mayesmaureend genelevelassociationanalysisofsystemicsclerosisacomparisonofafricanamericansandwhitepopulations |