Melanie E. Garrett
A5049761062- Hemoglobinopathies and Related Disorders
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Iron Metabolism and Disorders
- Stress Responses and Cortisol
- Birth, Development, and Health
- Bioinformatics and Genomic Networks
- Blood groups and transfusion
- Posttraumatic Stress Disorder Research
- Folate and B Vitamins Research
- Erythrocyte Function and Pathophysiology
- Genomics and Chromatin Dynamics
- Migration, Health and Trauma
- Attention Deficit Hyperactivity Disorder
- Single-cell and spatial transcriptomics
- Genetics and Neurodevelopmental Disorders
- Health, Environment, Cognitive Aging
- Tryptophan and brain disorders
- Child Abuse and Trauma
- Spinal Dysraphism and Malformations
- Liver Disease Diagnosis and Treatment
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Suicide and Self-Harm Studies
- Renal Diseases and Glomerulopathies
Duke University
2016-2025
Duke Medical Center
2016-2025
Durham VA Health Care System
2024
VA Mid-Atlantic Health Care Network
2024
Mental Illness Research, Education and Clinical Centers
2024
University of Utah
2023
Virginia Commonwealth University
2023
Huntsman (United States)
2023
QIMR Berghofer Medical Research Institute
2023
Duke University Hospital
2008-2021
Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments transcriptomic organization diseased brains are limited. In this work, we integrated genotypes RNA sequencing brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, bipolar disorder, as well controls. More than 25% the transcriptome exhibits differential splicing or expression,...
Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource adult brain across 1866 individuals. The contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles many cell types; quantitative-trait loci (QTLs); further QTLs associated with chromatin, splicing, cell-type...
Tobacco and alcohol use are heritable behaviours associated with 15% 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease injury1-4. These substances used across the globe, yet genome-wide association studies have focused on individuals European ancestries5. Here we leveraged global genetic diversity 3.4 million from four major clines ancestry (approximately 21% non-European) power discovery fine-mapping genomic loci tobacco use, inform function these via...
Clinicians rely upon the severity of liver fibrosis to segregate patients with well-compensated nonalcoholic fatty disease (NAFLD) into subpopulations at high- versus low-risk for eventual liver-related morbidity and mortality. We compared hepatic gene expression profiles in NAFLD identify processes that distinguish two groups hence might be novel biomarkers or treatment targets. Microarray analysis was used characterize percutaneous biopsies from low-risk, “mild” (fibrosis stage 0–1; n =...
Genes implicated in neuropsychiatric disorders are active human fetal brain, yet difficult to study a longitudinal fashion. We demonstrate that organoids from pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially genes and enhancers, with greatest changes occurring at transition stem progenitors. Networks of converging gene enhancer modules were assembled into six four global patterns...
In this study, the relationship of clinical differences among patients with sickle cell disease (SCD) was examined to understand major contributors early mortality in a contemporary cohort. Survival data were obtained for 542 adult subjects who enrolled since 2002 at three university hospitals southeast United States. Subjects followed up median 9.3 years. At enrollment, parameters collected, including hemoglobin (Hb) genotype, baseline laboratory values, comorbidities, and medication usage....
Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore mechanism non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals schizophrenia and 137 controls, 118,152 peaks. These accessible chromatin are highly enriched for SNP heritability. Accessible overlap...
Objective: This study investigated the role of self-regulation emotion in relation to functional impairment and comorbidity among children with without AD/HD. Method: A total 358 probands their siblings participated study, 74% sample participants affected by Parent-rated levels emotional lability served as a marker for emotion. Results: Nearly half AD/HD displayed significantly elevated versus 15% those this disorder. Children also higher rates impairment, comorbidity, treatment service...
Summary Renal failure occurs in 5–18% of sickle cell disease (SCD) patients and is associated with early mortality. At‐risk SCD cannot be identified prior to the appearance proteinuria pathobiology not well understood. The myosin, heavy chain 9, non‐muscle ( MYH9) apolipoprotein L1 APOL1) genes have been risk for focal segmental glomerulosclerosis end‐stage renal African Americans. We genotyped 26 single nucleotide polymorphisms (SNPs) MYH9 2 SNPs APOL1 (representing G1 G2 tags) 521...
Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) the most common subtype and complex trait with multigenic inheritance. Genome-wide association studies have previously identified significant between POAG SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p 3.87×10−11). plays role in ocular development has been associated morphology optic nerve. We sequenced coding regulatory regions 262 cases 256 controls six nonsynonymous variants, including five rare one...
Cellular heterogeneity in the human brain obscures identification of robust cellular regulatory networks, which is necessary to understand function non-coding elements and impact genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons glia with transcriptomic enhancer profiles, characterize gene landscape two major cell classes brain. We then leverage cell-type-specific landscapes gain insight into etiology several disorders. find that Alzheimer's...
Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD).
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study across ancestrally diverse individuals (European, African, Asian, Hispanic/Latino) from NHLBI Trans-Omics Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood variant genotype calling bioinformatic estimation in n = 109,122...
Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide study (GWAS) summary statistics, whole-genome sequences expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative using an optimal linear combination of statistics), to integrate eQTL dataset with multi-ancestry GWAS. By exploiting shared phenotypic effects...