Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the ...present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene-trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene-trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox.
The COVID-19 pandemic has heterogeneously affected use of basic health services worldwide, with disruptions in some countries beginning in the early stages of the emergency in March 2020. These ...disruptions have occurred on both the supply and demand sides of healthcare, and have often been related to resource shortages to provide care and lower patient turnout associated with mobility restrictions and fear of contracting COVID-19 at facilities. In this paper, we assess the impact of the COVID-19 pandemic on the use of maternal health services using a time series modelling approach developed to monitor health service use during the pandemic using routinely collected health information systems data. We focus on data from 37 non-governmental organisation-supported health facilities in Haiti, Lesotho, Liberia, Malawi, Mexico and Sierra Leone. Overall, our analyses indicate significant declines in first antenatal care visits in Haiti (18% drop) and Sierra Leone (32% drop) and facility-based deliveries in all countries except Malawi from March to December 2020. Different strategies were adopted to maintain continuity of maternal health services, including communication campaigns, continuity of community health worker services, human resource capacity building to ensure compliance with international and national guidelines for front-line health workers, adapting spaces for safe distancing and ensuring the availability of personal protective equipment. We employ a local lens, providing prepandemic context and reporting results and strategies by country, to highlight the importance of developing context-specific interventions to design effective mitigation strategies.
Background
The impact of safety‐net status, case volume, and outcomes among geriatric head and neck cancer patients is unknown.
Methods
Chi‐square tests and Student's t tests to compare head and neck ...surgery outcomes of elderly patients between safety‐net and non‐safety‐net hospitals. Multivariable linear regressions to determine predictors of outcome variables including mortality index, ICU stays, 30‐day readmission, total direct cost, and direct cost index.
Results
Compared with non‐safety‐net hospitals, safety‐net hospitals had a higher average mortality index (1.04 vs. 0.32, p = 0.001), higher mortality rate (1% vs. 0.5%, p = 0.002), and higher direct cost index (p = 0.001). A multivariable model of mortality index found the interaction between safety‐net status and medium case volume was predictive of higher mortality index (p = 0.006).
Conclusion
Safety‐net status is correlated with higher mortality index and cost in geriatric head and neck cancer patients. The interaction between medium volume and safety‐net status is independently predictive of higher mortality index.
Abstract
The use of external controls in genome-wide association study (GWAS) can significantly increase the size and diversity of the control sample, enabling high-resolution ancestry matching and ...enhancing the power to detect association signals. However, the aggregation of controls from multiple sources is challenging due to batch effects, difficulty in identifying genotyping errors and the use of different genotyping platforms. These obstacles have impeded the use of external controls in GWAS and can lead to spurious results if not carefully addressed. We propose a unified data harmonization pipeline that includes an iterative approach to quality control and imputation, implemented before and after merging cohorts and arrays. We apply this harmonization pipeline to aggregate 27 517 European control samples from 16 collections within dbGaP. We leverage these harmonized controls to conduct a GWAS of Crohn’s disease. We demonstrate a boost in power over using the cohort samples alone, and that our procedure results in summary statistics free of any significant batch effects. This harmonization pipeline for aggregating genotype data from multiple sources can also serve other applications where individual level genotypes, rather than summary statistics, are required.
Objective
The EuroQol 5‐Dimension (EQ‐5D) is a general health survey that is quick to administer, widely used, and directly convertible to health utility values (HUV). We aim to describe the ...five‐year EQ‐5D outcomes among patients who undergo surgical treatment for chronic rhinosinusitis (CRS).
Study Design
Prospective observational cohort study.
Methods
Patients with CRS completed the EQ‐5D questionnaire preoperatively and annually for five years following endoscopic sinus surgery. Paired t‐tests and McNemar's tests were used to compare preoperative and postoperative scores. Mixed‐effects modeling was used for multivariate analysis.
Results
Among 1296 patients enrolled in our study, 812 (74.7%) completed the postoperative survey at one year and 336 (38.9%) completed it at five years. There was a significant and sustained reduction of patients reporting pain/discomfort (74.9% vs. 58.0%, p < 0.001) and anxiety/depression (49.6% vs. 38.1%, p = 0.01) out to five years. Frequency of problems reported in the usual activity domain decreased at one year and was sustained through year four (30.6% vs 19.7%, p = 0.003). After multivariable modeling, female gender (p = 0.02), prior sinus surgery (p = 0.01), tobacco use (p = 0.038), headaches (p = 0.013), allergies (p = 0.001), diabetes (p = 0.022), hypertension (p = 0.036), higher preoperative SNOT‐22 score (p < 0.001), and a lower preoperative Lund‐Mackay score (p < 0.001) were associated with significantly worse EQ‐5D HUV over time. Similarly, a worse EQ‐5D Visual Analog Scale (VAS) over time was associated with allergies (p = 0.03), diabetes (p < 0.001), hypertension (p = 0.04), higher preoperative SNOT‐22 score (p < 0.001), and prior sinus surgery (p < 0.001).
Conclusion
Patients with chronic rhinosinusitis experience significant sustained improvements in health‐related quality of life up to five years after ESS as measured by the EQ‐5D instrument.
Level of Evidence
Level 2 Laryngoscope, 134:2592–2601, 2024
This study describes the five‐year EQ‐5D outcomes among patients who undergo surgical treatment for chronic rhinosinusitis (CRS). Patients with CRS experienced significant sustained improvements in health‐related quality of life up to five years after endoscopic sinus surgery as measured by the EQ‐5D instrument. These improvements were primarily driven by gains in the domains of pain/discomfort, anxiety/depression, and usual activity.
Synapses are fundamental information processing units of the brain and synaptic dysregulation is central to many brain disorders (‘synaptopathies’). However, systematic annotation of synaptic genes ...and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledgebase that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2922 annotations for 1112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variation associated with intelligence, educational attainment, ADHD, autism and bipolar disorder and among
de novo
variants associated with neurodevelopmental disorders including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis-platform for interpretation of large scale -omics data (
https://syngoportal.org
and
http://geneontology.org
).
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