Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Understanding Stakeholder Positionalities and Relationships to Reimagine Asylum at the US–Mexico Border: Observations from McAllen, TX

This paper draws on observational research conducted in McAllen, Texas, during the summer of 2019, of three major stakeholder groups involved in asylum management: Catholic Charities Humanitarian Respite Center (HRC); federal government agencies; and the McAllen community. Each group holds a unique, pluralistic perspective on migration, informing intra-group relations and exposing uneven power dynamics between them. Our analysis is contextualized by a local voice, a former long-term volunteer at the HRC, who speaks of the evolution of the McAllen border in her lifetime, as well as federal authority over McAllen and the HRC to process asylees. We dissect how this power dynamic produces a highly violent, detention-dominant immigration landscape in the Rio Grande Valley (RGV), antithetical to the practiced intersectional culture of voces locales. We reimagine how the US responds to asylum seekers by offering a community action-based framework, where these pluralistic perspectives are equitably valued. Based on interactions and conversations had with each group, we advocate a paradigm shift reflective of La Frontera’s (The Border’s) intersectional identity. This can be achieved by prioritizing voces locales and building capacity for the humanitarian sector, which is already doing critical work at the southern border. We look to contemporary movements like “Defund the Police” as examples, where divesting from the status-quo system of oppression can nurture reparative justice and empowerment to the RGV. In reimagining a more adaptive, asylum justice-oriented paradigm shift, we also recognize the need to abandon the government-controlled deterrence paradigm, which repeatedly causes tremendous harm