A5089202910- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Dementia and Cognitive Impairment Research
- Folate and B Vitamins Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Algal biology and biofuel production
- Substance Abuse Treatment and Outcomes
- Genomic variations and chromosomal abnormalities
- Adipokines, Inflammation, and Metabolic Diseases
- Neurotransmitter Receptor Influence on Behavior
- HIV Research and Treatment
- Herpesvirus Infections and Treatments
- Diatoms and Algae Research
- Genomics and Rare Diseases
- Gut microbiota and health
- Hepatitis B Virus Studies
- Cholinesterase and Neurodegenerative Diseases
- Natural product bioactivities and synthesis
- Hepatitis Viruses Studies and Epidemiology
- Complement system in diseases
Boston University
2018-2024
Alzheimer’s Disease Neuroimaging Initiative
2023
Jinan University
2012
Diatoms are important primary producers in the marine ecosystem. Currently it is difficult to genetically transform diatoms due technical limitations of existing methods. The promoter/terminator nitrate reductase gene model diatom Phaeodactylum tricornutum was cloned and used drive chloramphenicol acetyltransferase (CAT) reporter expression. construct transferred by electroporation into P. grown medium lacking silicon. CAT expression induced transformed presence nitrate, enabling growth...
Plastids are ideal subcellular hosts for the expression of transgenes and have been successfully used production different biopolymers, therapeutic proteins industrial enzymes. Phaeodactylum tricornutum is a widely aquatic feed species. In this study, we focused on developing high-efficiency plastid system P. tricornutum. transformation vector, site selected integration was transcriptionally active intergenic region present between trnI trnA genes, located in IR (inverted repeat) regions...
Variants in the APOE gene region may explain ethnic differences association of Alzheimer’s disease (AD) with ε4. Ethnic allele frequencies for three SNPs (single nucleotide polymorphisms) were identified and tested 19,398 East Asians (EastA), including Koreans Japanese, 15,836 European ancestry (EuroA) individuals, 4985 African Americans, brain imaging measures cortical atrophy sub-samples EuroAs. Among ε4/ε4 AD risk increased substantially a dose-dependent manner number promoter SNP...
Mechanisms underlying the protective effect of apolipoprotein E (APOE) ε2 against Alzheimer disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers. Complement pathway genes C4A and C4B were among most significantly differentially expressed between AD cases controls. also identified an ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes oligodendrocyte...
Abstract Introduction The genetic architecture of Alzheimer's disease (AD) is only partially understood. Methods We conducted an association study for AD using whole sequence data from 507 genetically enriched cases (i.e., having close relatives affected by AD) and 4917 cognitively healthy controls European ancestry (EA) 172 179 Caribbean Hispanic ancestry. Confirmation top findings stage 1 was sought in two family‐based genome‐wide sets a genome–sequencing set comprising members 42 EA 115...
Abstract Introduction The apolipoprotein E ( APOE ) ɛ2 allele reduces risk against Alzheimer's disease (AD) but mechanisms underlying this effect are largely unknown. Methods We conducted a genome‐wide association study for AD among 2096 carriers. potential role of the top‐ranked gene and complement 4 (C4) proteins, which were previously linked to in carriers, was investigated using human isogenic allele‐specific induced pluripotent stem cell (iPSC)–derived neurons astrocytes 224...
Blood-derived mitochondrial DNA copy number (mtDNA-CN) is a proxy measurement of function in the peripheral and central systems. Abnormal mtDNA-CN not only indicates impaired mtDNA replication transcription machinery but also dysregulated biological processes such as energy lipid metabolism. However, relationship between Alzheimer disease (AD) unclear. We performed two-sample Mendelian randomization (MR) using publicly available summary statistics from GWAS for AD to investigate causal AD....
Abstract INTRODUCTION Multiple infectious agents, including viruses, bacteria, fungi, and protozoa, have been linked to Alzheimer's disease (AD) risk by independent lines of evidence. We explored this association comparing the frequencies viral species identified in a large sample AD cases controls. METHODS DNA sequence reads that did not align human genome sequences were mapped reference sequences, quantified, then tested for with whole exome (WES) (WGS) datasets. RESULTS Several viruses...
Abstract Introduction Findings regarding the association between mitochondrial DNA (mtDNA) variants and Alzheimer's disease (AD) are inconsistent. Methods We developed a pipeline for accurate assembly variant calling in genomes embedded within whole exome sequences (WES) from 10,831 participants Disease Sequencing Project (ADSP). Association of AD risk was evaluated with each mtDNA located 1158 nuclear genes related to function using SCORE test. Gene‐based tests were performed SKAT‐O....
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...
Abstract Apolipoprotein ε4 ( APOE ε4) is the most significant genetic risk factor for late-onset Alzheimer’s disease (AD). Elevated blood C-reactive protein (CRP) further increases of AD people carrying allele. We hypothesized that CRP, as a key inflammatory element, could modulate impact other variants on risk. selected ten single nucleotide polymorphisms (SNPs) in reported loci encoding proteins related to inflammation. then tested interaction effects between these SNPs and CRP levels...
Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset the Alzheimer's Disease (AD) Genetics Consortium (ADGC) test for novel shared ancestry-specific AD susceptibility loci evaluate underlying genetic architecture 37,382 non-Hispanic White (NHW), 6,728 African American, 8,899 Hispanic (HIS), 3,232 East Asian individuals,...
Aim: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, to a lesser extent cocaine, contribute large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD CD, respectively). A genome-wide association study OD CD related phenotypes reflecting the time between first self-reported these substances DSM-IV diagnosis was conducted. Methods: Cox...
Background: Mitochondrial DNA (mtDNA) is a double-stranded circular and has multiple copies in each cell. Excess heteroplasmy, the coexistence of distinct variants mtDNA within cell, may lead to mitochondrial impairments. Accurate determination heteroplasmy whole-genome sequencing (WGS) data posed significant challenge because mitochondria carrying heteroplasmic cannot be distinguished during library preparation. Moreover, errors, contamination, nuclear segments can reduce accuracy variant...
Aim: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, to a lesser extent cocaine, contribute large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD CD, respectively). A genome-wide association study OD CD related phenotypes reflecting the time between first self-reported these substances DSM-IV diagnosis was conducted. Methods: Cox...
Abstract Mechanisms underlying the protective effect of apolipoprotein E ( APOE ) ε2 against Alzheimer’s disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 ε 2/ε 3 carriers. Complement pathway genes C4A and C4B were among most significantly differentially expressed between AD cases controls. also identified an ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes...
The study of DNA methylation quantitative trait loci (meQTLs) helps dissect regulatory mechanisms underlying genetic associations human diseases. In this study, we conducted the first genome-wide examination drivers variation in response to a triglyceride-lowering treatment with fenofibrate (response-meQTL) by using an efficient analytic approach.Subjects (n = 429) from GAW20 real data set genotype and both pre- (visit 2) post- 4) measurements were included. Following quality control steps...
Abstract Background In light of the complex etiology Alzheimer’s disease (AD), classifying AD patients into clinical subtypes is important for precision medicine. We tested whether polygenic risk scores (PRSs) combined with brain expression profiles in are correlated clinically defined subtypes. Methods generated 143 co‐expressed gene networks (modules) using RNA sequencing (RNA‐Seq) data derived from 64 autopsied brains Framingham Heart Study and Boston University Disease Center. These...
Some studies have reported that the gut microbiota can influence adrenal-related hormone levels. However, causal effects of on adrenal function remain unknown. Therefore, we employed a two-sample Mendelian randomization (MR) study to systematically investigate impact different regions gland. The summary statistics for and hormones used in MR analysis were derived from publicly available genome-wide association (GWAS). In analysis, inverse variance weighting (IVW) was as primary method, with...
Abstract Background Age is the largest risk factor for late‐onset Alzheimer’s Disease (LOAD). Although >80 genetic loci have been associated with LOAD, little known about age dependencies of these associations except APOE region. Method We performed cross‐ancestry and ancestry‐specific genome‐wide gene‐age interaction age‐stratified association study using TOPMed‐imputed (GWAS) data from Genetics Consortium (ADGC) including 34,833 non‐Hispanic Whites (NHW), 7,264 African Americans (AA),...
Abstract Background Several viruses have been linked to Alzheimer disease (AD) by independent lines of evidence. Method Whole genome and whole exome sequences (WGS/WES) derived from brain (3,404 AD cases, 894 controls) blood (15,612 24,544 obtained European ancestry (EU), African American (AA), Mexican (HMX), South Asian Indian (IND), Caribbean Hispanic (CH) participants the Alzheimer’s Disease Sequencing Project (ADSP) 276 cases 3,584 controls (all EU) Framingham Heart Study (FHS) that did...
Abstract Background With a rapidly aging population, South Korea anticipates surge in Alzheimer disease (AD). However, the genetic basis of AD Koreans is not well understood. Method We sequenced genomes 3,540 (1,583 cases and 1,957 controls) older than age 60 performed genome‐wide association study (GWAS) using logistic regression models that included covariates for age, sex, five ancestry principal components, an empirical relationship matrix. also conducted tests subgroups stratified by...
Abstract INTRODUCTION The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood. METHODS We performed an AD genome‐wide association study using whole‐genome sequence data from 3540 (1583 cases, 1957 controls) and single‐nucleotide polymorphism array 2978 Japanese (1336 1642 controls). Significant findings were evaluated by pathway enrichment differential gene expression analysis brain tissue controls cases with without dementia prior to death. RESULTS identified...
Numerous studies suggest that mitochondrial (MT) dysfunction is involved in Alzheimer disease (AD) pathogenesis. The Alzheimer's Disease Sequencing Project (ADSP) performed whole-exome sequencing (WES) of 5,519 AD cases and 4,917 cognitively normal elderly controls European ancestry (EA) 218 177 Caribbean Hispanic (CH) heritage. After mapping to the reference MT genome (NC_012920), variants were called using haploid mode GATK HaplotypeCaller. Low-quality, multi-allelic monomorphic excluded a...