Achilleas Pitsillides
A5010702001- Genetic Associations and Epidemiology
- Metabolomics and Mass Spectrometry Studies
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Cholesterol and Lipid Metabolism
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Genetic Syndromes and Imprinting
- Lipid metabolism and disorders
- Platelet Disorders and Treatments
- Cancer, Lipids, and Metabolism
- Genetic Mapping and Diversity in Plants and Animals
- Diabetes Treatment and Management
- Alzheimer's disease research and treatments
- Diet, Metabolism, and Disease
- Diabetes and associated disorders
- Lipid metabolism and biosynthesis
- Nutrition, Genetics, and Disease
- Antiplatelet Therapy and Cardiovascular Diseases
- Diabetes Management and Research
Boston University
2015-2025
Brigham and Women's Hospital
2023
Harbor–UCLA Medical Center
2023
Framingham Heart Study
2016-2022
National Heart Lung and Blood Institute
2016-2022
National Institutes of Health
2017
University of California, Davis
2017
University of Washington
2017
The University of Texas Health Science Center at Houston
2017
University of Mississippi Medical Center
2017
Abstract The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood sleep disorders, with ultimate goal improving diagnosis, treatment prevention these diseases. initial phases focused on whole-genome sequencing individuals rich phenotypic data diverse backgrounds. Here we describe TOPMed goals design as well available resources early insights obtained from sequence data. include a variant browser, genotype...
Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, sleep disorders, with ultimate goal improving diagnosis, treatment, prevention. initial phases focus on whole genome sequencing individuals rich phenotypic data diverse backgrounds. Here, we describe TOPMed goals design as well resources early insights from sequence data. include a variant browser, genotype imputation panel, sharing...
Abstract INTRODUCTION Genome‐wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire and captures rare variations, may GWAS METHODS We performed single common variant analysis aggregate analyses in pooled population ( N cases = 2184, controls 2383) targeted subpopulations using WGS data from Disease...
BackgroundPrior studies examined variants within presenilin-2 (PSEN2), presenilin-1 (PSEN1), and amyloid precursor protein (APP) genes. However, previously-reported clinically-relevant other predicted damaging missense (DM) have not been characterized in a newer release of the Alzheimer's Disease Sequencing Project (ADSP).ObjectiveTo characterize DM PSEN2, PSEN1, APP participants from ADSP.MethodsWe identified rare (MAF < 1%) 14,641 individuals with whole genome sequencing 16,849 exome...
Mitochondrial DNA (mtDNA) is present in multiple copies human cells. We evaluated cross-sectional associations of whole blood mtDNA copy number (CN) with several cardiometabolic disease traits 408,361 participants ancestries TOPMed and UK Biobank. Age showed a threshold association CN: among younger (<65 years age), each additional 10 age was associated 0.03 standard deviation (s.d.) higher level CN (P = 0.0014) versus 0.14 s.d. lower 1.82 × 10-13) older (≥65 years). At levels, we found...
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...
Abstract Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood and RNA sequencing expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis p < 1E−7 where the top most eGenes (i.e., transcripts a CpG) were enriched biological pathways related to cell signaling, for 1208 clinical...
Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods Results We performed cross-sectional prospective association analyses of blood-derived mtDNA CN outcomes in 27 316 participants 8 cohorts multiple racial ethnic groups with whole-genome sequencing. also Mendelian randomization to explore causal relationships coronary heart (CHD) cardiometabolic risk factors (obesity, diabetes, hypertension, hyperlipidemia).
OBJECTIVE To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a multiancestry time-to-event genome-wide association study CVD T2D. also tested 204 known coronary artery (CAD) variants CVD. RESULTS Among 49,230 participants T2D, 8,956 had events (event rate 18.2%). identified three novel loci CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10−9), rs77142250 HS3ST1,...
We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within Trans-Omics for Precision Medicine Program.We performed of cerebral and hippocampal volumes white matter hyperintensity (WMH) up 2,180 individuals testing rank-normalized residuals from mixed-effect linear regression models adjusted sex, age, total intracranial volume with individual while accounting familial relatedness....
Abstract To create a scientific resource of expression quantitative trail loci (eQTL), we conducted genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) DNA and gene levels RNA (RNA-seq) blood in 2622 participants Framingham Heart Study. We identified 6,778,286 cis -eQTL variant-gene transcript (eGene) pairs at p < 5 × 10 –8 (2,855,111 unique variants 15,982 eGenes) 1,469,754 trans variant-eGene 1e−12 (526,056 7233 eGenes). In addition, 442,379...
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...
DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify quantitative trait loci (mQTLs) in 4126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) P < 1e-7 and 33,572,145 trans-mQTL variant-CpG 213,606 1e-14. Using cis-mQTL variants 1258 CpGs associated with seven cardiovascular disease...
Single nucleotide polymorphisms (SNPs) located in the chromosomal region 16p13.13 have been previously associated with risk for several autoimmune diseases, including type 1 diabetes. To identify and localize specific variants diabetes this understand mechanism of their action, we resequenced a 455-kb diabetic patients unaffected control subjects, identifying 93 novel variants. A panel 939 SNPs that included 46 these was genotyped 3,070 multiplex families Forty-eight SNPs, all CLEC16A,...
Abstract Risk for late-onset Alzheimer’s disease (LOAD) is driven by multiple loci primarily identified genome-wide association studies, many of which are common variants with minor allele frequencies (MAF)> 0.01. To identify additional and rare LOAD risk variants, we performed a GWAS on 25,170 subjects 41,052 cognitively normal controls in 44 datasets from the International Genomics Project (IGAP). Existing genotype data was imputed using dense, high-resolution Haplotype Reference...
Background: The widely held assumptions that in type 1 diabetes glucose variability may correlate with insulin sensitivity and impaired epinephrine counterregulation have not been studied directly. Here we investigate possible relationships between outpatient measures of risk for hypoglycemia physiological characteristics: counterregulation. Methods: Thirty-four subjects (14 women, 20 men; 37 ± 2.1 years old; glycosylated hemoglobin [HbA1c], 7.6 0.21%) performed self-monitoring blood (SMBG)...
Prior studies using the ADSP data examined variants within presenilin-2 (PSEN2), presenilin-1 (PSEN1), and amyloid precursor protein (APP) genes. However, previously-reported clinically-relevant other predicted damaging missense (DM) have not been characterized in a newer release of Alzheimer's Disease Sequencing Project (ADSP).
Summary Inhibition of platelet reactivity is a common therapeutic strategy in secondary prevention cardiovascular disease. Genetic and environmental factors influence inter-individual variation reactivity. Identifying genes that contribute to can reveal new biological mechanisms possible targets. Here, we examined rare coding identify associated with population-based cohort. To do so, performed whole exome sequencing the Framingham Heart Study conducted single variant gene-based association...