Publications by authors named "Tyler Kinzy"

Article Synopsis
  • * By analyzing data from the Million Veteran Program and other cohorts, the study identifies 63 genetic loci linked to AMD, including 30 that were previously unknown, highlighting significant differences in risk among various ancestries.
  • * The findings reveal that certain genetic risk factors, like those found in the CFH locus, have varying effects based on ancestry, suggesting that targeted therapies could be developed by considering these genetic differences.
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Importance: Primary open-angle glaucoma (POAG) polygenic risk scores (PRSs) continue to be evaluated in primarily European-ancestry populations despite higher prevalence and worse outcomes in African-ancestry populations.

Objective: To evaluate how established POAG PRSs perform in African-ancestry samples from the Genetics in Glaucoma Patients of African Descent (GIGA), Genetics of Glaucoma in Individuals of African Descent (GGLAD), and Million Veteran Program (MVP) datasets and compare these with European-ancestry samples.

Design, Setting, And Participants: This was a multicenter, cross-sectional study of POAG cases and controls from Tanzania, South Africa, Nigeria, Ghana, and the US.

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Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance.

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Although glaucoma is a disease modulated by eye pressure, the mechanisms of pressure sensing in the eye are not well understood. Here, we investigated associations between mechanosensitive ion channel gene variants and primary open-angle glaucoma (POAG). Common (minor allele frequency > 5%) single nucleotide polymorphisms located within the genomic regions of 20 mechanosensitive ion channel genes in the K2P, TMEM63, PIEZO and TRP channel families were assessed using genotype data from the NEIGHBORHOOD consortium of 3853 cases and 33,480 controls.

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Purpose: Genetic variants in regions that include the mitochondrial genes thioredoxin reductase 2 (TXNRD2) and malic enzyme 3 (ME3) are associated with primary open-angle glaucoma (POAG) in genome-wide association studies (GWASs). To assess their clinical impact, we investigated whether TXNRD2 and ME3 genetic risk scores (GRSs) are associated with specific glaucoma phenotypes.

Design: Cross-sectional study.

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Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common glaucoma subtype, is more prevalent and severe in individuals of African ancestry. Unfortunately, this ancestral group has been historically under-represented among genetic studies of POAG.

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A major goal of precision medicine is to stratify patients based on their genetic risk for a disease to inform future screening and intervention strategies. For conditions like primary open-angle glaucoma (POAG), the genetic risk architecture is complicated with multiple variants contributing small effects on risk. Following the tepid success of genome-wide association studies for high-effect disease risk variant discovery, genetic risk scores (GRS), which collate effects from multiple genetic variants into a single measure, have shown promise for disease risk stratification.

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Importance: Tobacco 21 (T21) policies raise the minimum legal age to purchase tobacco from 18 to 21 years to curb youth access to tobacco products. While some studies have found that T21 is associated with reducing prevalence of youth tobacco use, little is known about the impact it may have on youth of different racial and ethnic identities.

Objective: To evaluate the association of T21 policy with the prevalence of high school youth tobacco use across sex, race, and ethnicity.

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Purpose: Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification.

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The availability of electronic health record (EHR)-linked biobank data for research presents opportunities to better understand complex ocular diseases. Developing accurate computable phenotypes for ocular diseases for which gold standard diagnosis includes imaging remains inaccessible in most biobank-linked EHRs. The objective of this study was to develop and validate a computable phenotype to identify primary open-angle glaucoma (POAG) through accessing the Department of Veterans Affairs (VA) Computerized Patient Record System (CPRS) and Million Veteran Program (MVP) biobank.

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Objective: To explore the role of several genetic polymorphisms (APOE ε4, BDNF Met, and COMT Val) in executive functioning performance in patients with pharmacoresistant temporal lobe epilepsy (TLE).

Methods: Ninety-three adults (51 female, mean age = 39 years) with TLE completed executive functioning measures as part of a comprehensive preoperative neuropsychological evaluation, including Trail Making Test (Part B), Wisconsin Card Sorting Test (Conceptual Level Responses and Perseverative Errors), Color Word Interference from the Delis Kaplan Executive Function System, and measures of phonemic and semantic verbal fluency. Genotyping of the APOE, BDNF, and COMT genes was conducted using DNA extracted from peripheral blood or brain tissue (from epilepsy surgery).

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Glaucoma leads to millions of cases of visual impairment and blindness around the world. Its susceptibility is shaped by both environmental and genetic risk factors. Although over 120 risk loci have been identified for glaucoma, a large portion of its heritability is still unexplained.

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Background: Continuous tracking of ambulatory activity in real-world settings using step activity monitors has many potential uses. However, feasibility, accuracy, and correlation with performance measures in stroke patients have not been well-established.

Objective: The primary study objective was to determine adherence with wearing a consumer-grade step activity monitor, the Fitbit Charge HR, in home-going ischemic stroke patients during the first 90 days after hospital discharge.

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Background: Age-related macular degeneration (AMD) is a progressive retinal disease contributing to blindness worldwide. Multiple estimates for AMD heritability (h) exist; however, a substantial proportion of h is not attributable to known genomic loci. The International AMD Genomics Consortium (IAMDGC) gathered the largest dataset of advanced AMD (ADV) cases and controls available and identified 34 loci containing 52 independent risk variants defining known AMD h.

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Introduction: Patient-centered care, particularly shared medical decision making, is difficult to measure in critically ill patients where decisions are often made by a designated surrogate, often receiving information from multiple providers with varying degrees of training. The purpose of this study was to compare short-term satisfaction with care and decision making in patients or surrogates between two neurocritical care units [one staffed by a neurocritical care attending and advanced practice providers (APPs) and one staffed by a neurocritical care attending and resident/fellow trainees] using the Family Satisfaction in the ICU (FS-ICU) survey.

Methods: Over a 6-month period, the FS-ICU was administered on a tablet device to patients or surrogates at least 24 h after admission and stored on REDCap database.

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Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.

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Return of results is not common in research settings as standards are not yet in place for what to return, how to return, and to whom. As a pioneer of large-scale of return of research results, the Precision Medicine Initiative Cohort now known of All of Us plans to return pharmacogenomic results and variants of clinical significance to its participants starting late 2019. To better understand the local landscape of possibilities regarding return of research results, we assessed the frequency of pathogenic variants and APOL1 renal risk variants in a small diverse cohort of chronic kidney disease patients (CKD) ascertained from a public hospital in Cleveland, Ohio genotyped on the Illumina Infinium MegaEX.

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Genome-wide variation data with millions of genetic markers have become commonplace. However, the potential for interpretation and application of these data for clinical assessment of outcomes of interest, and prediction of disease risk, is currently not fully realized. Many common complex diseases now have numerous, well-established risk loci and likely harbor many genetic determinants with effects too small to be detected at genome-wide levels of statistical significance.

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Purpose: Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability.

Methods: We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating.

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Methods for exploring genetic interactions have been developed in an attempt to move beyond single gene analyses. Because biological molecules frequently participate in different processes under various cellular conditions, investigating the changes in gene coexpression patterns under various biological conditions could reveal important regulatory mechanisms. One of the methods for capturing gene coexpression dynamics, named liquid association (LA), quantifies the relationship where the coexpression between two genes is modulated by a third "coordinator" gene.

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Introduction: Very little quantitative data on occupational burnout and exposure to critical incidents are available from contemporary United States emergency medical services (EMS) cohorts. Given that burnout has been associated positively with turnover intentions and absenteeism in EMS workers, studies that uncover correlates of burnout may be integral to combating growing concerns around retention in the profession.

Methods: We administered a 167-item electronic survey that included the Maslach Burnout Inventory (MBI) and a modified version of the Critical Incident History Questionnaire (n=29 incident types) to paramedics, emergency medical technicians (EMTs), and dispatchers of a single ambulance service.

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Objectives: To examine the accuracy of general health cross-walk tables in a clinical sample of patients with spine disorders. Published tables (Schalet BD, Rothrock NE, Hays RD, et al. Linking physical and mental health summary scores from the Veterans RAND 12-Item Health Survey (VR-12) to the PROMIS(®) Global Health Scale.

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Background: Sexual dysfunction is a common symptom of multiple sclerosis (MS) that often goes unreported by both the patient and the clinician. Sexual dysfunction can affect a person's mood, relationships, daily functioning, and quality of life. Gaining a better understanding of the prevalence and nature of sexual dysfunction in individuals with MS would not only help identify patients with this problem but also determine contributing factors, which can inform treatment alternatives available to the patient.

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