Amanda Dobbyn
A5041572980- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Genetic Syndromes and Imprinting
- Bipolar Disorder and Treatment
- Bioinformatics and Genomic Networks
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Stress Responses and Cortisol
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Eating Disorders and Behaviors
- Data Analysis with R
- Single-cell and spatial transcriptomics
- Health, Environment, Cognitive Aging
- Heat shock proteins research
- Functional Brain Connectivity Studies
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
Icahn School of Medicine at Mount Sinai
2015-2023
Abstract The availability of high-quality RNA-sequencing and genotyping data post-mortem brain collections from consortia such as CommonMind Consortium (CMC) the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) enable generation a large-scale cis- eQTL meta-analysis. Here we generate cerebral cortical 1433 samples available four cohorts (identifying >4.1 million significant >18,000 genes), well cerebellar 261 874,836 >10,000 genes). We find substantially improved...
Hereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations carrying variant, its effect other ancestry populations including Hispanic/Latino individuals, and rates achieving a diagnosis carriers are unknown.To assess association between identify hATTR-CM among with failure.Cross-sectional analysis noncarriers aged 50 years or...
Integrating rare variation from trio family and case-control studies has successfully implicated specific genes contributing to risk of neurodevelopmental disorders (NDDs) including autism spectrum (ASD), intellectual disability (ID), developmental (DDs), epilepsy (EPI). For schizophrenia (SCZ), however, while sets have been through the study variation, only two identified.We used hierarchical Bayesian modeling rare-variant genetic architecture estimate mean effect sizes risk-gene...
ABSTRACT Bipolar disorder is a highly heritable psychiatric that features episodes of mania and depression. We performed the largest genome-wide association study to date, including 20,352 cases 31,358 controls European descent, with follow-up analysis 822 sentinel variants at loci P<1×10 -4 in an independent sample 9,412 137,760 controls. In combined analysis, 30 reached significant evidence for association, which 20 were novel. These contain genes encoding ion channels neurotransmitter...
Abstract Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of protein-coding regions genome identified causal role for ten genes concentration rare variant signals evolutionarily constrained 1 . This study—and other large-scale human genetics studies—was mainly composed individuals European (EUR) ancestry, generalizability findings non-EUR populations remains unclear. To address this gap, we...
Large genome-wide association studies (GWAS) have identified many genetic loci associated with risk for myocardial infarction (MI) and coronary artery disease (CAD). Concurrently, efforts such as the National Institutes of Health (NIH) Roadmap Epigenomics Project Encyclopedia DNA Elements (ENCODE) Consortium provided unprecedented data on functional elements human genome. In present study, we systematically investigate biological link between variants this complex their impacts gene...
To reveal post-traumatic stress disorder (PTSD) genetic risk influences on tissue-specific gene expression, we use brain and non-brain transcriptomic imputation. We impute genetically regulated expression (GReX) in 29,539 PTSD cases 166,145 controls from 70 ancestry-specific cohorts identify 18 significant GReX-PTSD associations corresponding to specific tissue-gene pairs. The results suggest substantial heterogeneity based ancestry, cohort type (military versus civilian), sex. Two...
Objective There is no evidence for a genetic association between organic anion transporters 1–3 ( SLC22A6, SLC22A7, and SLC22A8 ) multidrug resistance protein 4 (MRP4; encoded by ABCC4 with the levels of serum urate or gout. The Māori Pacific (Polynesian) population New Zealand has highest prevalence gout worldwide. aim this study was to determine whether any Polynesian population–specific variants in SLC22A6–8 are associated Methods All participants had ≥3 self‐reported and/or grandparents....
Tissue-specific genetic features in multiple tissues can inform prediction of drug side effects clinical trials.
Abstract Structural variants (SVs) contribute to many disorders, yet, functionally annotating them remains a major challenge. Here, we integrate SVs with RNA-sequencing from human post-mortem brains quantify their dosage and regulatory effects. We show that genic exist at significantly lower frequencies than intergenic SVs. Functional impact of copy number (CNVs) stems both the proportion content altered loss-of-function intolerance gene. train linear model predict expression effects rare...
Abstract Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls European ancestry, which identified 64 associated genomic loci. risk alleles were enriched in genes synaptic signaling pathways brain-expressed genes, particularly those high specificity expression neurons the prefrontal cortex hippocampus. Significant signal enrichment was found encoding targets antipsychotics, calcium...
Abstract Multiplex families with a high prevalence of psychiatric disorder are often examined to identify rare genetic variants large effect sizes. In the present study, we analysed whether risk for bipolar (BD) in BD multiplex is influenced by common variants. Furthermore, investigated this conferred mainly BD-specific or also associated susceptibility schizophrenia major depression. total, 395 individuals from 33 Andalusian (166 BD, 78 depressive disorder, 151 unaffected) as well 438...
Abstract Background Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the genetic variants disease. Transcriptomic imputation (TI) allows translation those into regulatory mechanisms, which can then be used to assess functional outcome genetically regulated gene expression (GReX) in broader setting through use phenome-wide (pheWASs)...
Joint analysis of multiple traits can result in the identification associations not found through each trait isolation. Studies neuropsychiatric disorders and congenital heart disease (CHD) which use de novo mutations (DNMs) from parent-offspring trios have reported putatively causal genes. However, a joint method designed to integrate DNMs studies has yet be implemented. We here introduce multiple-trait TADA (mTADA) jointly analyzes two using non-overlapping family samples. first...