A5054682287- Genetic Associations and Epidemiology
- Parathyroid Disorders and Treatments
- Genomics and Rare Diseases
- Bone health and treatments
- Genetics and Neurodevelopmental Disorders
- Vitamin D Research Studies
- COVID-19 Clinical Research Studies
- Liver Disease Diagnosis and Treatment
- Folate and B Vitamins Research
- Diabetes and associated disorders
- HIV, Drug Use, Sexual Risk
- Opioid Use Disorder Treatment
- SARS-CoV-2 and COVID-19 Research
- Substance Abuse Treatment and Outcomes
- Adipokines, Inflammation, and Metabolic Diseases
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Genomic variations and chromosomal abnormalities
- Genetic Mapping and Diversity in Plants and Animals
- Personality Disorders and Psychopathology
- Cardiovascular Disease and Adiposity
- Nasolacrimal Duct Obstruction Treatments
- Renal cell carcinoma treatment
- RNA Research and Splicing
- Metabolomics and Mass Spectrometry Studies
- Gestational Diabetes Research and Management
Vanderbilt University Medical Center
2019-2024
Vanderbilt University
2020-2024
Vanderbilt Health
2023
Abstract Background Clinical laboratory (lab) tests are used in clinical practice to diagnose, treat, and monitor disease conditions. Test results stored electronic health records (EHRs), a growing number of EHRs linked patient DNA, offering unprecedented opportunities query relationships between genetic risk for complex quantitative physiological measurements collected on large populations. Methods A total 3075 lab were extracted from Vanderbilt University Medical Center’s (VUMC) EHR system...
Abstract The major anxiety disorders (ANX; including generalized disorder, panic and phobias ) are highly prevalent, often onset early, persist throughout life, cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases 729,881 controls. We identified 58 independent...
Abstract T-cells play a critical role in multiple aspects of human health and disease. However, to date the genetic determinants T-cell abundance have not been studied at scale because assays quantifying are widely used clinical or research settings. The complete blood count assay quantifies lymphocyte which includes T-cells, B-cells, NK-cells. To address this gap, we directly estimate fractions from whole genome sequencing data over 200,000 individuals multi-ethnic TOPMed All Us studies. We...
Opioid use disorders (OUDs) constitute a major public health issue, and we urgently need alternative methods for characterizing risk OUD. Electronic records (EHRs) are useful tools understanding complex medical phenotypes but have been underutilized OUD because of challenges related to underdiagnosis, binary diagnostic frameworks, minimally characterized reference groups. As first step in addressing these challenges, new paradigm is warranted that characterizes opioid prescription misuse on...
Abstract Clinical laboratory (lab) tests are used in clinical practice to diagnose, treat, and monitor disease conditions. Test results typically stored electronic health records (EHRs), a growing number of EHRs linked patient DNA, offering unprecedented opportunities query relationships between lab genetics. data, however, uneven quality, previous studies have focused on small traits. We present two methods, QualityLab LabWAS, clean analyze EHR labs at scale Lab-Wide Association Scan. In...
Abstract Background People hospitalized with COVID-19 often exhibit hematological alterations, such as lower lymphocyte and platelet counts, which have been reported to associate disease prognosis. It is unclear whether inter-individual variability in baseline parameters prior acute infection influences risk of SARS-CoV-2 progression severe COVID-19. Methods We assessed the association blood cell counts indices incident UK Biobank Vanderbilt University Medical Center Synthetic Derivative...
Dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high-grade tumors. However, it remains unclear whether single nucleotide polymorphisms (SNPs) that alter the sensitivity calcium-sensing receptor (CaSR) to circulating are associated primary and/or secondary neoplasms at specific pathological sites European and African ancestry. Multivariable logistic regression models were used analyze association CASR SNPs calcium, parathyroid hormone, vitamin...
Fibromyalgia is a complex disease of unclear etiology that complicated by difficulties in diagnosis, treatment, and clinical heterogeneity. To clarify this etiology, healthcare-based data are leveraged to assess the influences on fibromyalgia several domains. Prevalence less than 1% females our population register data, about 1/10th males. often presents with co-occurring conditions including back pain, rheumatoid arthritis, anxiety. More comorbidities identified hospital-associated biobank...
Abstract Environmental and genetic risk factors contribute to the development of borderline personality disorder (BPD). We conducted largest GWAS BPD date, meta-analyzing data from 12,339 cases 1,041,717 controls European ancestry, identified six independent associated genomic loci, nine genes in gene-based analysis. observed a single-nucleotide polymorphism (SNP) heritability 17.3% derived polygenic scores (PGS) predicted 4.6% phenotypic variance case-control status. showed strongest...
Abstract Purpose Dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high grade tumors. However, it remains unclear whether single nucleotide polymorphisms (SNPs) that alter the sensitivity calcium-sensing receptor (CaSR) to circulating are associated primary and/or secondary neoplasms at specific pathological sites European and African ancestry. Methods Multivariable logistic regression models were used analyze association CASR SNPs calcium,...
12063 Background: Platinum levels are measurable in the serum for decades after cisplatin therapy and higher may be related to chemotherapy-induced toxicities. Since is cleared exclusively by kidney, we hypothesized that a genetic predictor of kidney function, an estimated glomerular filtration rate polygenic risk score (eGFR PRS), would significantly associate with platinum could improve prediction models. Methods: Within large well-characterized, multicenter clinical cohort...
To enable large-scale application of polygenic risk scores (PRSs) in a computationally efficient manner, we translate widely used PRS construction method, PRS–continuous shrinkage, to the Julia programming language, PRS.jl. On nine different traits with varying genetic architectures, demonstrate that PRS.jl maintains accuracy prediction while decreasing average runtime by 5.5×. Additional programmatic modifications improve usability and robustness. This freely available software...
Abstract Cancer-induced hypercalcemia (CIH) is common in cancer patients with metastatic disease and up to 30% of breast cases without evidence metastasis. During malignancy, tumor cells-including triple negative (TNBC) cells, secrete factors such as parathyroid hormone-related protein (PTHrP) that causes the osteolysis. As progresses, it becomes inevitable increase cell derived PTHrP associated persistent osteolysis, leads a progressive systemic calcium (Ca2+) or CIH. The resulting...
ABSTRACT Background Electronic health records (EHR) are useful tools for understanding complex medical phenotypes, but they have been underutilized opioid use disorders (OUD). Patterns of prescription might provide an objective measure OUD risk. Methods We extracted data over 2.6 million patients across three registries (Vanderbilt University Medical Center, Mass General Brigham, Geisinger) between 2005 and 2018. defined groups based on levels exposure: No Prescription, Minimal Exposure (2...
The calcium sensing receptor (CaSR) is a ubiquitously expressed G-protein coupled known to be major sensor in most tissues and organ systems. It regulate systemic homeostasis by slight increases influencing the secretion of parathyroid hormone chief cells. Unfortunately, CaSR invariably mutated inactivating mutations particular, are associated with development cancer-induced hypercalcemia (CIH). Among several CASR polymorphisms described thus far, rs1801725 (A986S SNP) common among Caucasian...
Abstract The calcium sensing receptor (CaSR) is a ubiquitously expressed G-protein coupled known to be major sensor in most tissues and organ systems. It regulate systemic homeostasis by slight increases influencing the secretion of parathyroid hormone chief cells. Unfortunately, CaSR invariably mutated inactivating mutations particular, are associated with development cancer-induced hypercalcemia (CIH). Among several CASR polymorphisms described thus far, rs1801725 (A986S SNP) common among...
To determine the impact of autoimmunity in absence glycemic alterations on pregnancy type 1 diabetes (T1D).
Abstract The dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high-grade tumors. associated comorbidity known as cancer-induced hypercalcemia (CIH) which affects up to 30% cases, the absence metastasis. In course breast cancer progression, secretion parathyroid hormone-related protein (PTHrP) by tumor cells and destruction bone tissues, leads a progressive increase or CIH. circulating Ca2+ sensed calcium-sensing receptor (CaSR), plays...