11 research outputs found
Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
All authors: Olga Y. Gorlova ,
Yafang Li,
Ivan Gorlov,
Jun Ying,
Wei V. Chen,
Shervin Assassi,
John D. Reveille,
Frank C. Arnett,
Xiaodong Zhou,
Lara Bossini-Castillo,
Elena Lopez-Isac,
Marialbert Acosta-Herrera,
Peter K. Gregersen,
Annette T. Lee,
Virginia D. Steen,
Barri J. Fessler,
Dinesh Khanna,
Elena Schiopu,
Richard M. Silver,
Jerry A. Molitor,
Daniel E. Furst,
Suzanne Kafaja,
Robert W. Simms,
Robert A. Lafyatis,
Patricia Carreira,
Carmen Pilar Simeon,
Ivan Castellvi,
Emma Beltran,
Norberto Ortego,
Christopher I. Amos,
Javier Martin,
Maureen D. Mayes.Data Availability Statement: Genetic data is
available from dbGaP repository (https://www.ncbi.
nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_
id=phs000357.v1.p1).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.Funding was provided to MDM by the National Institutes of Health (NIH) the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS https://www.niams.nih.gov/) Centers of Research Translation (CORT) P50-AR054144, NIH grant N01-AR-02251 and R01-AR-055258, and the Department of Defense (DD) Congressionally Directed Medical Research Program (http://cdmrp.army.mil/) W81XWH-07-1-011 and WX81XWH-13-1-0452 for the collection, analysis and interpretation of the data
Eigenvalues of the transition matrix A of the state-space model for the genes in a regulatory network responding to silica in cultured human normal and SSc fibroblasts.
<p>Eigenvalues of the transition matrix A of the state-space model for the genes in a regulatory network responding to silica in cultured human normal and SSc fibroblasts.</p
State-space model for the regulatory gene network responding to silica stimulation in cultured human fibroblasts.
<p>The numbers next to the edges are the coefficients in the state-space equations for the normal (black color) and SSc (red color) fibroblasts, respectively. The numbers in the boxes denote the mean expression values of the genes in normal (black color) and SSc (red color) fibroblasts.</p
Root-locus of gene expression in normal fibroblasts.
<p>Root-locus of gene expression in normal fibroblasts.</p
Frequencies of different ECG findings and their impact on mortality in the GENISOS cohort.
<p>Frequencies of different ECG findings and their impact on mortality in the GENISOS cohort.</p
Characteristics of patients with and without ECG abnormalities in the GENISOS Study Population.
<p>Characteristics of patients with and without ECG abnormalities in the GENISOS Study Population.</p
Association of ECG findings with low ejection fraction and elevated right ventricular systolic pressure on echocardiogram.
<p>Association of ECG findings with low ejection fraction and elevated right ventricular systolic pressure on echocardiogram.</p
Genes most significant (at p<10<sup>−3</sup>) in African Americans in the gene-level analysis and the results for these genes in Whites, based on ImmunoChip.
<p>Genes most significant (at p<10<sup>−3</sup>) in African Americans in the gene-level analysis and the results for these genes in Whites, based on ImmunoChip.</p
Comparison of novel candidate genes (at p<4.35x10<sup>-6</sup> indicated in bold) and suggestive genes (4.35x10<sup>-6</sup>−5) detected in Whites to the corresponding statistics in African Americans in the gene level analysis, based on ImmunoChip.
<p>Comparison of novel candidate genes (at p<4.35x10<sup>-6</sup> indicated in bold) and suggestive genes (4.35x10<sup>-6</sup>−5) detected in Whites to the corresponding statistics in African Americans in the gene level analysis, based on ImmunoChip.</p