Admixture mapping of coronary artery calcification in African Americans from the NHLBI family heart study

BACKGROUND: Coronary artery calcification (CAC) is an imaging biomarker of coronary atherosclerosis. In European Americans, genome-wide association studies (GWAS) have identified several regions associated with coronary artery disease. However, few large studies have been conducted in African Americans. The largest meta-analysis of CAC in African Americans failed to identify genome-wide significant variants despite being powered to detect effects comparable to effects identified in European Americans. Because CAC is different in prevalence and severity in African Americans and European Americans, admixture mapping is a useful approach to identify loci missed by GWAS. RESULTS: We applied admixture mapping to the African American cohort of the Family Heart Study and identified one genome-wide significant region on chromosome 12 and three potential regions on chromosomes 6, 15, and 19 that are associated with CAC. Follow-up studies using previously reported GWAS meta-analysis data suggest that the regions identified on chromosome 6 and 15 contain variants that are possibly associated with CAC. The associated region on chromosome 6 contains the gene for BMP-6, which is expressed in vascular calcific lesions. CONCLUSIONS: Our results suggest that admixture mapping can be a useful hypothesis-generating tool to identify genomic regions that contribute to complex diseases in genetically admixed populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0196-x) contains supplementary material, which is available to authorized users

The Generational Fight for Affirmative Equality: Understanding and Dismantling the Assault on Affirmative Action

The Generational Fight for Affirmative Equality: Understanding and Dismantling the Assault on Affirmative Action by Leewana Thomas, Kiah Zellner-Smith, Aaron Brink-Johnson, Felicia Johnson, Isela Gomez , Jocelyne Cardona , Maya Vilaplana, Ryan Brownlow, Whitney Zilton,and Grace Zaima

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento del Magdalena.

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento del Magdalena.El presente trabajo es producto del Diplomado de Acompañamiento de acción Psicosocial en el escenarios de violencia, se sustenta en la búsqueda de la comprensión y el análisis contextual pormenorizado a partir de la integración de procesos académicos que articulan teorías, metodologías y técnicas para el diagnóstico, acompañamiento y evaluación de situaciones traumáticas, crisis y violencias a las que se ve expuesta una persona, grupo o institución. La primera actividad se realiza de manera individual, eligiendo un caso descrito para analizarlo y luego realizar un ejercicio respondiendo preguntas que lo llevan a comprender más la temática de violencia hacia un individuo y la manera cómo afronta los problemas físicos, psicológicos y sociales. Luego de manera colaborativa se realiza un análisis de un caso en particular donde relatan el caso de una comunidad que afronta problemas de conflicto armado y las consecuencias de la misma; abordando problemáticas psicosociales generados por el desplazamiento, muerte, inclusión social, todos inherentes al conflicto armado. Teniendo en cuenta los contenidos propuestos en las unidades prácticas, en el presente trabajo del Diplomado de profundización en escenarios de violencia se abarcan los contextos del enfoque narrativo, los cuales se trabajaron en distintos casos tomado de VOCES: Relatos de violencia y esperanza en Colombia, Editado por el Banco mundial en el año 2009,entre estos; Sé tomó el “caso de Carlos Arturo”, escogido por su gran importancia e impacto generado como resultado de víctimas de violencia en las minas anti personas, cambiando su vida completamente, mientras que en el caso propuesto en la Guía de Actividades “los pobladores de Cacarica” resalta los hechos violentos que vivieron estos pobladores, los cuales fueron obligados a desplazarse, dejando sus tierras dejando atrás sus sueños, con el fin de analizar, valorar y comprender los eventos psicosociales traumáticos desde una perspectiva psicológica, Los emergentes psicosociales aún siguen afectando a la población después de la violencia, permitiendo realizar un abordaje psicosocial, mediante el enfoque narrativo, el análisis de los relatos, las técnicas, acciones y por último las estrategias, argumentado por diferentes actores.The present work is the product of the Diploma of Accompanying of Psychosocial action in the scenarios of violence, it is based on the search for detailed understanding and contextual analysis based on the integration of academic processes that articulate theories, methodologies and techniques for diagnosis, accompanying and evaluation of traumatic situations, crises and violence to which a person, group or institution is exposed. The first activity is carried out individually, choosing a case described to analyze it and then perform an exercise answering questions that lead you to understand more the issue of violence towards an individual and the way he addresses physical, psychological and social problems. Then, in a collaborative way, an analysis of a particular case is carried out where it reports the case of a community that faces problems of armed conflict and its consequences; addressing psychosocial issues generated by displacement, death, social inclusion, all inherent in the armed conflict. Taking into account the contents proposed in the practical units, in the present work of the Diploma of deepening in scenarios of violence the contexts of the narrative approach are covered, which they worked on different cases taken from VOCES: Stories of violence and hope in Colombia, Edited by the World Bank in 2009, among these; they took the "case of Carlos Arturo", chosen for its great importance and impact generated as a result of victims of violence from anti-people mines, changing their lives completely, while in the case proposed in the Activities Guide "the inhabitants of Cacarica ”highlights the violent events that these settlers experienced, who were forced to move, leaving their lands leaving behind their dreams, in order to analyze, assess and understand traumatic psychosocial events from a psychological perspective. The purpose of this work is to analyze and understand them from our psychological perspective, seeking that emerging psychosocials still affect the population after the violence, allowing a psychosocial approach, through the narrative approach, the analysis of the stories, the techniques, actions and finally the strategies, argued by different participants

Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303

Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas mutation burden was significantly higher in relapsed/refractory (rel/ref) FL and t-FL than in newly diagnosed (dx) FL. Nonetheless, mutation burden in dx FL was not associated with frontline progression-free survival (PFS). CREBBP was the only gene more commonly mutated in FL than in t-FL yet mutated CREBBP was associated with shorter frontline PFS in FL. Mutations in 20 genes were more common in rel/ref FL or t-FL than in dx FL, including 6 significantly mutated genes (SMGs): STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. We defined a mutations associated with progression (MAP) signature as ≥2 mutations in these 7 genes (6 rel/ref FL or t-FL SMGs plus CREBBP). Patients with dx FL possessing a MAP signature had shorter frontline PFS, revealing a 7-gene set offering insight into FL progression risk potentially more generalizable than the m7-Follicular Lymphoma International Prognostic Index (m7-FLIPI), which had modest prognostic value in our cohort. Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients

Ultra-deep sequencing reveals the mutational landscape of classical Hodgkin lymphoma

UNLABELLED: The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified \u3e95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL. SIGNIFICANCE: Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient

Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) $(p = 8.8×10^{−7} and p = 1.5×10^{−6}$ respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels $(p = 13.5×10^{−12})$. The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report