Amanda B. Kuzma
A5039340118- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Genomics and Phylogenetic Studies
- Nutrition, Genetics, and Disease
- Health, Environment, Cognitive Aging
- Genomic variations and chromosomal abnormalities
- Biological Research and Disease Studies
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Biomedical Text Mining and Ontologies
- Neurological diseases and metabolism
- Ethics in Clinical Research
- Parkinson's Disease Mechanisms and Treatments
- Cancer Genomics and Diagnostics
- Dementia and Cognitive Impairment Research
- Machine Learning in Bioinformatics
- Inflammation biomarkers and pathways
- Genetics and Neurodevelopmental Disorders
- Genetics, Bioinformatics, and Biomedical Research
- Artificial Intelligence in Healthcare and Education
- Frailty in Older Adults
- Topic Modeling
- Folate and B Vitamins Research
Advocate Health Care
2025
University of Pennsylvania
2016-2024
Penn Center for AIDS Research
2022-2023
Genomics (United Kingdom)
2022
University of Miami
2017
Dr. John T. Macdonald Foundation
2017
Abstract INTRODUCTION Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Disease (ACAD) was formed to address underrepresentation of Asians research, and limited understanding how genetics non‐genetic/lifestyle factors impact this multi‐ethnic population. METHODS ACAD started fully recruiting October 2021 with one central coordination site, eight recruitment sites, two analysis sites. We developed comprehensive...
Abstract INTRODUCTION Alzheimer's disease (AD) is a common disorder of the elderly that both highly heritable and genetically heterogeneous. METHODS We investigated association AD with variants aggregates rare coding non‐coding in 13,371 individuals diverse ancestry whole genome sequencing (WGS) data. RESULTS Pooled‐population analyses all identified genetic at apolipoprotein E ( APOE ) BIN1 associated p < 5 × 10 −8 ). Subgroup‐specific haplotype on chromosome 14 including PSEN1...
The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site Genomics Database (GenomicsDB) is a public knowledge base disease (AD) genetic datasets and genomic annotations.
Abstract Summary We report VCPA, our SNP/Indel Variant Calling Pipeline and data management tool used for the analysis of whole genome exome sequencing (WGS/WES) Alzheimer’s Disease Sequencing Project. VCPA consists two independent but linkable components: pipeline tracking database. The pipeline, implemented using Workflow Description Language fully optimized Amazon elastic compute cloud environment, includes steps from aligning raw sequence reads to variant calling GATK. database allows...
Summary Work in the past 10 years has greatly expanded our understanding of Alzheimer's disease (AD) genetics, with more than 20 susceptibility genetic loci discovered large genome‐wide association and sequencing studies. The NIA Genetics Disease Data Storage Site (NIAGADS) is funded by National Institute on Aging to serve as a one‐stop portal for community access research data findings generated from AD genetics projects. In this article, we describe mission NIAGADS, available resources,...
Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation generating high-quality SV call set from the Alzheimer’s Disease Sequencing Project comprising 578 individuals 111 families. Employing two complementary pipelines, Scalpel Parliament, SV/indel we assessed through sample replicates (N = 9) with silico spike-ins. developed novel metric,...
Annotation of genomic variants is an increasingly important and complex part the analysis sequence-based analyses. Computational predictions variant function are routinely incorporated into gene-based analyses rare-variants, though to date most studies use limited information for assessing that often agnostic disease being studied.
Most of the loci identified by genome-wide association studies (GWAS) for late-onset Alzheimer's disease (LOAD) are in strong linkage disequilibrium (LD) with nearby variants all which could be actual functional variants, often non-protein-coding regions and implicating underlying gene regulatory mechanisms. We set out to characterize causal mechanisms, tissue contexts, target genes these associations. applied our INFERNO algorithm top 19 non-APOE from IGAP GWAS study. annotated LD-expanded...
Alzheimer's Disease (AD) is a common disorder of the elderly that both highly heritable and genetically heterogeneous. Here, we investigated association between AD variants aggregates rare coding noncoding in 13,371 individuals diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic or near APOE, BIN1, LINC00320 significantly associated (p < 5×10-8). Population-specific haplotype on chromosome 14 including PSEN1 Hispanics, further supported by...
The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to joint analysis. Here we bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen centers Alzheimer's Disease Sequencing Project. joint-genotype called variant-called format (VCF) file contains only positions within union kits. VCF was then processed specifically account batch effects arising from use different...
<title>Abstract</title> Health systems face the challenge of balancing innovation and safety to responsibly implement artificial intelligence (AI) solutions. The rapid proliferation, growing complexity, ethical considerations, rising demand for these tools require timely efficient processes rigorous evaluation ongoing monitoring. Current AI frameworks often lack practical guidance health address challenges. To fill this gap, we developed a prescriptive governance framework informed by...
<b><i>Background/Aims:</i></b> The Alzheimer’s Disease Sequencing Project (ADSP) aims to identify novel genes influencing disease (AD). Variants within known cause dementias other than AD have previously been associated with risk. We describe evidence of co-segregation and associations between variants in dementia clinically diagnosed the ADSP. <b><i>Methods:</i></b> summarize properties pathogenic genes, annotated as “pathogenic” ClinVar new...
Recent Alzheimer's disease (AD) genetics findings from genome-wide association studies (GWAS) span progressively larger and more diverse populations outcomes. Currently, there is no up-to-date resource providing harmonized searchable information on all AD genetic associations found by GWAS, nor linking the reported variants genes with functional genomic annotations.
Rich data from large biobanks, coupled with increasingly accessible association statistics genome-wide studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method perform polygenic score-based biobank-wide scans. Compared traditional approaches, BADGERS uses GWAS summary as input does not require multiple be measured in same cohort. applied two independent datasets for late-onset Alzheimer's disease...
Abstract Progressive supranuclear palsy (PSP) is a rare Parkinsonian disorder characterized by problems with movement, balance, cognition, and other symptoms. PSP differs from Alzheimer’s disease (AD) neurodegenerative diseases displaying abnormal forms of the microtubule-associated protein tau (“tauopathies”) presence pathology not only in neurons, but also astrocytes oligodendrocytes. Genetic contributors may mediate these differences, however much genetics remains unexplained. Here we...
Abstract Up to 80% of Parkinson's disease patients develop dementia, but time dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents clinical features similar Parkinson’s cognitive impairment precedes or coincides It remains controversial whether and are distinct conditions represent part a spectrum. The biological mechanisms underlying heterogeneity, in particular the development remain poorly understood, will likely be key understanding pathways and,...
Alzheimer’s Disease (AD) is a progressive neurologic disease and the most common form of dementia. While causes AD are not completely understood, genetics plays key role in etiology AD, thus finding genetic factors holds potential to uncover novel mechanisms. For this study, we focus on copy number variation (CNV) detection burden analysis. Leveraging whole-genome sequence (WGS) data released by Sequencing Project (ADSP), developed scalable bioinformatics pipeline identify CNVs. This was...
Abstract Rich data from large biobanks, coupled with increasingly accessible association statistics genome-wide studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method perform polygenic score-based biobank-wide scans. Compared traditional approaches, BADGERS uses GWAS summary as input does not require multiple be measured in same cohort. applied two independent datasets for late-onset...
Abstract Due to methodological reasons, the X-chromosome has not been featured in major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) 115,841 AD cases or proxy cases, including 52,214 clinically-diagnosed 613,671 controls. We considered three approaches account for different inactivation (XCI) states females, i.e. random XCI, skewed escape XCI....
The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of and Related Dementias (AD/ADRD) by sequencing whole genomes affected participants age-matched cognitive controls from diverse populations. Genome Center for (GCAD) processed whole-genome data 36,361 ADSP participants, including 35,014 genetically unique which 45% are non-European ancestry, across 17 cohorts in 14 countries this fourth release (R4). This effort identified 387...