Gene-level association analysis of systemic sclerosis : A comparison of African-Americans and White populations
Gorlova, Olga Y. (Dartmouth College)
Li, Yafang (Dartmouth College)
Gorlov, Ivan (Dartmouth College)
Ying, Jun (University of Texas McGovern Medical School)
Chen, Wei V. (UT MD Anderson Cancer Center)
Assassi, Shervin (University of Texas McGovern Medical School)
Reveille, John D. (University of Texas McGovern Medical School)
Arnett, Frank C. (University of Texas McGovern Medical School)
Zhou, Xiaodong (University of Texas McGovern Medical School)
Bossini-Castillo, Lara (Wellcome Trust Sanger Institute (Regne Unit))
Lopez-Isac, Elena (Institute of Parasitology and Biomedicine López-Neyra)
Acosta-Herrera, Marialbert (Institute of Parasitology and Biomedicine López-Neyra)
Gregersen, Peter K. (Feinstein Institute for Medical Research)
Lee, Annette T. (Robert S. Feinstein Institute for Medical Research)
Steen, Virginia D. (Georgetown University Medical Center)
Fessler, Barri J. (University of Alabama-Birmingham)
Khanna, Dinesh (University of Michigan)
Schiopu, Elena (University of Michigan)
Silver, Richard M. (Medical University of South Carolina)
Molitor, Jerry A. (University of Minnesota)
Furst, Daniel E. (University of Florence)
Kafaja, Suzanne (University of California-Los Angeles)
Simms, Robert W. (Boston University)
Lafyatis, Robert A. (University of Pittsburgh)
Carreira, Patricia E (Hospital Universitario de Madrid)
Simeón-Aznar, Carmen Pilar (Hospital Universitari Vall d'Hebron)
Castellvi, Ivan (Institut d'Investigació Biomèdica Sant Pau)
Beltran, Emma (Hospital Universitari i Politècnic La Fe (València))
Ortego, Norberto (Hospital Universitario San Cecilio (Granada))
Amos, Christopher I. (Dartmouth College)
Martin, Javier (Institute of Parasitology and Biomedicine López-Neyra. IPBLN-CSIC)
Mayes, Maureen D. (University of Texas McGovern Medical School)
Universitat Autònoma de Barcelona

Fecha:	2018
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	African Continental Ancestry Group ; European Continental Ancestry Group ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; Scleroderma, Systemic
Publicado en:	PloS one, Vol. 13 Núm. 1 (january 2018) , p. e0189498, ISSN 1932-6203

DOI: 10.1371/journal.pone.0189498
PMID: 29293537

12 p, 1.3 MB

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