The Relationship Between Social Vulnerability and COVID-19 Incidence Among Louisiana Census Tracts

Objective: To examine the association between the Centers for Disease Control and Prevention (CDC)\u27s Social Vulnerability Index (SVI) and COVID-19 incidence among Louisiana census tracts. Methods: An ecological study comparing the CDC SVI and census tract-level COVID-19 case counts was conducted. Choropleth maps were used to identify census tracts with high levels of both social vulnerability and COVID-19 incidence. Negative binomial regression with random intercepts was used to compare the relationship between overall CDC SVI percentile and its four sub-themes and COVID-19 incidence, adjusting for population density. Results: In a crude stratified analysis, all four CDC SVI sub-themes were significantly associated with COVID-19 incidence. Census tracts with higher levels of social vulnerability were associated with higher COVID-19 incidence after adjusting for population density (adjusted RR: 1.52, 95% CI: 1.41-1.65). Conclusions: The results of this study indicate that increased social vulnerability is linked with COVID-19 incidence. Additional resources should be allocated to areas of increased social disadvantage to reduce the incidence of COVID-19 in vulnerable populations

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

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity

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

Abstract: 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

Aberrant DNA Methylation in Human iPSCs Associates with MYC-Binding Motifs in a Clone-Specific Manner Independent of Genetics

Induced pluripotent stem cells (iPSCs) show variable methylation patterns between lines, some of which reflect aberrant differences relative to embryonic stem cells (ESCs). To examine whether this aberrant methylation results from genetic variation or non-genetic mechanisms, we generated human iPSCs from monozygotic twins to investigate how genetic background, clone, and passage number contribute. We found that aberrantly methylated CpGs are enriched in regulatory regions associated with MYC protein motifs and affect gene expression. We classified differentially methylated CpGs as being associated with genetic and/or non-genetic factors (clone and passage), and we found that aberrant methylation preferentially occurs at CpGs associated with clone-specific effects. We further found that clone-specific effects play a strong role in recurrent aberrant methylation at specific CpG sites across different studies. Our results argue that a non-genetic biological mechanism underlies aberrant methylation in iPSCs and that it is likely based on a probabilistic process involving MYC that takes place during or shortly after reprogramming

Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells.

In this study, we used whole-genome sequencing and gene expression profiling of 215 human induced pluripotent stem cell (iPSC) lines from different donors to identify genetic variants associated with RNA expression for 5,746 genes. We were able to predict causal variants for these expression quantitative trait loci (eQTLs) that disrupt transcription factor binding and validated a subset of them experimentally. We also identified copy-number variant (CNV) eQTLs, including some that appear to affect gene expression by altering the copy number of intergenic regulatory regions. In addition, we were able to identify effects on gene expression of rare genic CNVs and regulatory single-nucleotide variants and found that reactivation of gene expression on the X chromosome depends on gene chromosomal position. Our work highlights the value of iPSCs for genetic association analyses and provides a unique resource for investigating the genetic regulation of gene expression in pluripotent cells

Toward principles for enhancing the resilience of ecosystem services

A major challenge of the twenty-first century is ensuring an adequate and reliable flow of essential ecosystem services (ES) to meet the needs of a burgeoning world population. All social-ecological systems (SES) produce a “bundle” of ES, including provisioning (e.g., freshwater, crops, meat), regulating (e.g., flood and climate regulation), and cultural services (e.g., recreation, spiritual values). Extensive and rapid global changes, including urbanization, growing human populations, rising consumption, and increased global connections, have led to a large and growing demand for provisioning services. Meeting these needs has resulted in large-scale conversion of natural ecosystems to cropland, which has eroded the capacity of ecosystems to produce other ES essential to human health and security—especially regulating services. Furthermore, extensive anthropogenic changes to the world's ecosystems are increasing the likelihood of large, nonlinear, and potentially irreversible changes, such as coral reef degradation. Such events often have substantial and sometimes catastrophic impacts on ES and human well-being