Albert Vernon Smith

IntroductionBlood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.MethodsHere, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.ResultsOur analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation (P < 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature …

People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP‐C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3–6 months (October‐2014 to November‐2019). Participants eligible for this analysis included those at‐risk of HCV primary infection (anti‐HCV negative) or re‐infection (anti‐HCV positive, HCV RNA negative) with follow‐up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person‐years of follow‐up). Overall HCV incidence was 6.11/100 person‐years (95%CI: 5.07–7.35), with higher rate of re‐infection (9.34/100 person‐years; 95%CI: 7.15–12.19) than primary infection (4.60/100 person‐years; 95%CI: 3 …

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We …

Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data. Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP (n = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg (n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg (n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American). Results: One variant in the known HTN locus, KCNK3, was a top finding in the multi-ethnic analysis (p = 8.23E-07) for the normotensive control group [rs12476527, odds ratio (95% confidence interval) = 0.80 (0.74–0.88)]. This variant was replicated in the Vanderbilt University Medical Center’s DNA repository data. Aggregate gene-based signals included the genes AGTPBP …

Background Acquired pulmonary artery pseudoaneurysm (PAP) is a rare but potentially lethal condition caused by penetrating trauma. Definitive diagnosis requires computed tomography angiography (CTA) demonstrating saccular or fusiform areas of dilatation with homogenous contrast filling which occurs simultaneously with the pulmonary artery. The lesions are treated by endovascular repair or surgery. Swift diagnosis and treatment are vital due to the high risk of mortality in the event of rupture. Case Description A 16 year old male arrived to the trauma bay as a transfer with a gunshot wound (GSW) to the right upper quadrant and a right-sided chest tube with 600 cc bloody output. He was hypotensive and was taken to the operating room for emergent exploratory laparotomy, which was negative. Postoperative CT demonstrated a 2.2 x3. 9 region of contained extravasation in the upper lobe of the right lung …

Background:The COVID-19 pandemic continues to pose challenges for healthcare systems across the world. Many patients infected with the virus, whether mild or severe, have nutritional complications ranging from poor appetite to the need for nutrition support. Limited research has shown that nutritional status plays a significant role in disease outcomes for COVID-19 patients. Although the American Society for Parenteral and Enteral Nutrition set guidelines for the nutritional management of COVID-19 patients, to date there are few major studies investigating the association between nutritional risk and outcomes in these patients. Thus, the purpose of this study is to assess the association between nutritional status and outcomes in hospitalized patients with COVID-19 and to identify the most common feeding practices among these patients. Method (s) A descriptive research design was used. Researchers reviewed the medical records of a random sample of 300 adult patients diagnosed with COVID-19 admitted to an academic metropolitan healthcare system between March 2020 to March 2021. Nutritional status was obtained from the admission screening and assessment documentation by a clinical dietitian (RD). Patients were then stratified based on admission nutritional status as malnourished or not. Differences in hospital length of stay (LOS), ICU LOS, ventilator dependence (in hours), and mortality were compared between groups using Mann-Whitney U, independent t-test, and chi-square tests. Result (s) Malnourished patients had a longer median (IQR) length of stay compared to non-malnourished patients (8 days (3, 16) vs 4 days (3, 8 …

The human leukocyte antigen (HLA) locus is associated with more complex diseases than any other locus in the human genome. In many diseases, HLA explains more heritability than all other known loci combined. In silico HLA imputation methods enable rapid and accurate estimation of HLA alleles in the millions of individuals that are already genotyped on microarrays. HLA imputation has been used to define causal variation in autoimmune diseases, such as type I diabetes, and in human immunodeficiency virus infection control. However, there are few guidelines on performing HLA imputation, association testing, and fine mapping. Here, we present a comprehensive tutorial to impute HLA alleles from genotype data. We provide detailed guidance on performing standard quality control measures for input genotyping data and describe options to impute HLA alleles and amino acids either locally or using the …

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian …