Social and Polygenic Risk Factors for Time to Comorbid Diagnoses in Individuals with Substance Use Disorders: A Phenome-Wide Survival Analysis.

Importance: Persons with substance use disorders (SUD) often suffer from additional comorbidities, including psychiatric conditions and physical health problems. Researchers have explored this overlap in electronic health records (EHR) using phenome wide association studies (PheWAS) to characterize how different indicators are related to all conditions in an individual's EHR. However, analyses have been largely cross-sectional in nature.

Biological Insights from Schizophrenia-associated Loci in Ancestral Populations.

Large-scale genome-wide association studies of schizophrenia have uncovered hundreds of associated loci but with extremely limited representation of African diaspora populations. We surveyed electronic health records of 200,000 individuals of African ancestry in the Million Veteran and All of Us Research Programs, and, coupled with genotype-level data from four case-control studies, realized a combined sample size of 13,012 affected and 54,266 unaffected persons. Three genome-wide significant signals - near , , and - are the first to be independently identified in populations of predominantly African ancestry.

Detecting and Adjusting for Hidden Biases due to Phenotype Misclassification in Genome-Wide Association Studies.

With the advent of healthcare-based genotyped biobanks, genome-wide association studies (GWAS) leverage larger sample sizes, incorporate patients with diverse ancestries and introduce noisier phenotypic definitions. Yet the extent and impact of phenotypic misclassification on large-scale datasets is not currently well understood due to a lack of statistical methods to estimate relevant parameters from empirical data. Here, we develop a statistical method and scalable software, PheMED, Phenotypic Measurement of Effective Dilution, to quantify phenotypic misclassification across GWAS using only summary statistics.

Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System.

Importance: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide.

Objective: To benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies.

Design, Setting, And Participants: Extensive Veterans Health Administration's electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found.

The inflammasome pathway: A key player in ocular surface and anterior segment diseases.

Inflammasomes are multicomplex molecular regulators with an emerging importance in regulating ocular surface and anterior segment health and disease. Key components found in the eye include NF-κB, NLRP3, NLRC4, NLRP6, ASC, IL-1β, IL-18, and caspase-1. The role of NLRP1, NLRC4, AIM2, and NLRP3 inflammasomes in the pathogenesis of infectious ulcers, DED, uveitis, glaucoma, corneal edema, and other diseases is being studied with many developments.

Impact of Ocular Surface Temperature on Tear Characteristics: Current Insights.

Infrared (IR) thermographic assessment of ocular surface temperature (OST) is gaining interest as an adjuvant method to evaluate the ocular surface. It is a quick, non-invasive test that causes minimal, if any, discomfort to patients. The purpose of this article was to summarize research on how OST relates to tear film parameters and dry eye disease (DED).

Impact of Air Pollution and Weather on Dry Eye.

Air pollution has broad effects on human health involving many organ systems. The ocular surface is an excellent model with which to study the effects of air pollution on human health as it is in constant contact with the environment, and it is directly accessible, facilitating disease monitoring. Effects of air pollutants on the ocular surface typically manifest as dry eye (DE) symptoms and signs.

Indoor Airborne Microbial Concentration and Dry Eye.

Purpose: To examine associations between indoor airborne microbial concentration and dry eye (DE) measures.

Design: Prospective, observational, cross-sectional study.

Methods: A total of 157 individuals with normal external ocular anatomy were recruited from the Miami Veterans Affairs eye clinic.

Association of the Indoor Environment With Dry Eye Metrics.

Importance: The ocular surface is continuously exposed to the environment. Although studies have focused on associations between outdoor environmental conditions and dry eye, information on associations between the indoor environment and dry eye is lacking.

Objective: To determine associations between the indoor environment and dry eye.

Genome-wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder.

Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations.

Human Ocular Surface Particulate Composition in the Clinical Versus Home Environment.

Purpose: Our eyes are chronically exposed to airborne particulate matter shown to adversely affect the ocular surface. This research examines size, type (organic vs. inorganic), and elemental composition of particles recovered from the ocular surface in 2 environments and their associations with dry eye (DE) metrics.

Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms.

Dysfunctional coping behaviors, such as catastrophizing, have been implicated in pain severity and chronicity across several pain disorders. However, the impact of dysfunctional coping has not been examined under the context of dry eye (DE). This study evaluates relationships between catastrophizing and measures of DE, including pain severity and pain-related daily interference.

Impact of seasonal variation in meteorological conditions on dry eye severity.

Purpose: To compare dry eye (DE) diagnosis patterns by season in Miami vis-a-vis the US and examine differences in DE symptoms and signs by season in Miami.

Patients And Methods: US veteran affairs (VA) patient visits with ICD-9 codes for DE (375.15) and routine medical examination (V70.

Adult human periodontal ligament-derived stem cells delay retinal degeneration and maintain retinal function in RCS rats.

Background: Retinal degeneration (RD) is a leading cause of irreversible blindness, affecting millions of people worldwide. Stem cell transplantation has been considered a promising therapy for retinal degenerative diseases. This study aimed to investigate the therapeutic potential of human periodontal ligament-derived stem cells (hPDLSCs) for intervention in the progress of this degeneration in the Royal College Surgeons (RCS) rat.

Impact of genotyping errors on statistical power of association tests in genomic analyses: A case study.

A key step in genomic studies is to assess high throughput measurements across millions of markers for each participant's DNA, either using microarrays or sequencing techniques. Accurate genotype calling is essential for downstream statistical analysis of genotype-phenotype associations, and next generation sequencing (NGS) has recently become a more common approach in genomic studies. How the accuracy of variant calling in NGS-based studies affects downstream association analysis has not, however, been studied using empirical data in which both microarrays and NGS were available.

Cardiomyogenesis of periodontal ligament-derived stem cells by dynamic tensile strain.

Cellular therapies for the treatment of myocardial infarction have proven to be an invaluable tool in recent years and provide encouraging evidence for the possibility to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. This study explores the use of a population of stem cells arising from the neural crest and isolated from adult human periodontal ligament along with short-term mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for cellular cardiomyoplasty.

The genetics of functional disability in schizophrenia and bipolar illness: Methods and initial results for VA cooperative study #572.

Given the prominence of cognitive impairments and disability associated with schizophrenia and bipolar disorder, substantial interest has arisen in identifying determinants of the diseases and their features. Genetic variation has been linked to skills that underlie disability ("functional capacity" or FC), highlighting need for understanding of these relationships. We describe the design and methods of a large, multisite, observational study focusing on the genetics of functional disability in schizophrenia and bipolar disorder, presenting initial data on recruitment, and characterization of the sample.