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Institution

Veterans Health Administration

GovernmentWashington D.C., District of Columbia, United States
About: Veterans Health Administration is a government organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Veterans Affairs. The organization has 63820 authors who have published 98417 publications receiving 4835425 citations. The organization is also known as: VHA.


Papers
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Journal ArticleDOI
TL;DR: It is reported that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I Interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS.
Abstract: We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 x 10(-11)), IRF8 (P = 3.73 x 10(-9)) and CD6 (P = 3.79 x 10(-9)). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio = 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency = 0.02; odds ratio = 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS.

788 citations

Journal ArticleDOI
TL;DR: It is demonstrated that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.
Abstract: Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.

787 citations

Journal ArticleDOI
Lam C. Tsoi1, Sarah L. Spain2, Sarah L. Spain1, Jo Knight1  +212 moreInstitutions (52)
TL;DR: A meta-analysis of genome-wide association studies and independent data sets genotyped on the Immunochip identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals, and identified five independent signals within previously known loci.
Abstract: To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

786 citations

Journal ArticleDOI
28 Feb 2007-JAMA
TL;DR: Prolonged exposure is an effective treatment for PTSD in female veterans and active-duty military personnel and it is feasible to implement prolonged exposure across a range of clinical settings.
Abstract: ContextThe prevalence of posttraumatic stress disorder (PTSD) is elevated among women who have served in the military, but no prior study has evaluated treatment for PTSD in this population. Prior research suggests that cognitive behavioral therapy is a particularly effective treatment for PTSD.ObjectiveTo compare prolonged exposure, a type of cognitive behavioral therapy, with present-centered therapy, a supportive intervention, for the treatment of PTSD.Design, Setting, and ParticipantsA randomized controlled trial of female veterans (n=277) and active-duty personnel (n=7) with PTSD recruited from 9 VA medical centers, 2 VA readjustment counseling centers, and 1 military hospital from August 2002 through October 2005.InterventionParticipants were randomly assigned to receive prolonged exposure (n = 141) or present-centered therapy (n = 143), delivered according to standard protocols in 10 weekly 90-minute sessions.Main Outcome MeasuresPosttraumatic stress disorder symptom severity was the primary outcome. Comorbid symptoms, functioning, and quality of life were secondary outcomes. Blinded assessors collected data before and after treatment and at 3- and 6-month follow-up.ResultsWomen who received prolonged exposure experienced greater reduction of PTSD symptoms relative to women who received present-centered therapy (effect size, 0.27; P = .03). The prolonged exposure group was more likely than the present-centered therapy group to no longer meet PTSD diagnostic criteria (41.0% vs 27.8%; odds ratio, 1.80; 95% confidence interval, 1.10-2.96; P = .01) and achieve total remission (15.2% vs 6.9%; odds ratio, 2.43; 95% confidence interval, 1.10-5.37; P = .01). Effects were consistent over time in longitudinal analyses, although in cross-sectional analyses most differences occurred immediately after treatment.ConclusionsProlonged exposure is an effective treatment for PTSD in female veterans and active-duty military personnel. It is feasible to implement prolonged exposure across a range of clinical settings.Trial Registrationclinicaltrials.gov Identifier: NCT00032617

784 citations

Journal ArticleDOI
TL;DR: Risk for negative outcomes may be modified by both genetic and environmental factors, with the quality and availability of social supports among the most important environmental factors in promoting resiliency in maltreated children, even in the presence of a genotype expected to confer vulnerability for psychiatric disorder.
Abstract: In this study, measures of the quality and availability of social supports were found to moderate risk for depression associated with a history of maltreatment and the presence of the short (s) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR). The present investigation (i) replicates research in adults showing that 5-HTTLPR variation moderates the development of depression after stress, (ii) extends the finding to children, and (iii) demonstrates the ability of social supports to further moderate risk for depression. Maltreated children with the s/s genotype and no positive supports had the highest depression ratings, scores that were twice as high as the non-maltreated comparison children with the same genotype. However, the presence of positive supports reduced risk associated with maltreatment and the s/s genotype, such that maltreated children with this profile had only minimal increases in their depression scores. These findings are consistent with emerging preclinical and clinical data suggesting that the negative sequelae associated with early stress are not inevitable. Risk for negative outcomes may be modified by both genetic and environmental factors, with the quality and availability of social supports among the most important environmental factors in promoting resiliency in maltreated children, even in the presence of a genotype expected to confer vulnerability for psychiatric disorder.

782 citations


Authors

Showing all 63886 results

NameH-indexPapersCitations
Michael Karin236704226485
Paul M. Ridker2331242245097
Eugene Braunwald2301711264576
Ralph B. D'Agostino2261287229636
John Q. Trojanowski2261467213948
Fred H. Gage216967185732
Edward Giovannucci2061671179875
Rob Knight2011061253207
Frank E. Speizer193636135891
Stephen V. Faraone1881427140298
Scott M. Grundy187841231821
Paul G. Richardson1831533155912
Peter W.F. Wilson181680139852
Dennis S. Charney179802122408
Kenneth C. Anderson1781138126072
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202314
2022137
20216,161
20205,712
20195,171
20184,497