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• scRNAseq of patients with chronic graft-versus-host-disease

  This dataset contains 10 samples from 9 patients with chronic graft-versus-host disease (GVHD). Each sample is analysed with Chromium V(D)J and 5' Gene Expression Platform v1.1 (10X Genomics). The raw data includes fastq files for Gene expression and fastq files for V(D)J Expression. The processed data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-13419.

  Dataset EGAD00001012121

• Determinants of Venetoclax Resistance

  The study aimed to identify genetic determinants of resistance to Venetoclax, a recently approved BCL-2 inhibitor for patients with chronic lymphocytic leukemia (CLL). Whole exome sequencing of tumor samples from 6 CLL patients relapsing on Venetoclax revealed clonal evolution when comparing pre- and post-Venetoclax samples. Genetic screens for genes involved in sensitivity to Venetoclax and investigations of resistant cell lines (including OCI-Ly1) revealed MCL-1 and regulators of cellular energy metabolism (AMPK pathway) to drive resistance to Venetoclax. Further explorations of patient samples confirmed MCL-1 expression and AMPK activation to be increased at relapse on Venetoclax.

  Study phs001875

• Genetics of Pigmentation in Eastern and Southern African Populations Study

  The goal of this study was to identify genes and loci associated with pigmentation in African populations. It comprises 1,593 participants from Ethiopia, Tanzania, and Botswana. Sexes are evenly represented (768 males and 825 females) and self reported ages ranged from 18 to 103. Mean age was used for individuals without ages. For each participant, a DSM II color meter was used to measure underarm skin reflectance in triplicate. These measures averaged and converted to a melanin index (MI = 100 x log10(1/(x/255)). All individuals were included in a genome wide scan that accounted for age, sex, and genetic relatedness.

  Study phs001396

• Single Cell Transcriptomic Data from CD4+ T Cells from Children with MIS-C

  Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections in the pediatric population characterized by fever, multi-organ involvement and systemic inflammation. Single-cell RNA sequencing was used to evaluate the transcriptomic signature of CD4+ T cells obtained from the peripheral blood of patients with MIS-C before (n=3) and after (n=5) immunomodulatory treatment, along with pediatric controls (n=4). Compared to controls and treated children with MIS-C, T cells obtained from pre-treatment MIS-C patients upregulated genes associated with activation, such as NF-kB signaling. This single-cell transcriptomic data was used in the context of a larger study entitled, "Notch1-CD22-Dependent Immune Dysregulation in the SARSCoV2-Associated Multisystem Inflammatory Syndrome in Children."

  Study phs003086

• Impact of Race and Genetic Factors on Beta Blocker Effectiveness in Heart Failure

  Heart Failure (HF) continues to be an enormous public health problem, despite the many advances in its pharmacotherapy over the past 25 years. The availability of multiple therapeutic options for HF requires individualization of therapy. However, there are currently insufficient tools to guide the optimal selection of therapy. The expansion of human genomic information has led to exciting new opportunities to improve the selection of drug therapy. In order to evaluate whether genetic variation impacts outcomes and drug response in heart failure, we performed a cohort study of patients with heart failure. Our overall plan was to recruit patients who have heart failure and receive treatment through HAP-HFMG. This allowed us to collect clinical outcomes, and quantify medication adherence via electronic pharmacy claims data. We collected whole blood samples for genetic analysis. We then tested whether genetic variants can predict patient outcomes (survival) in the context of their medical therapy (drug exposure). The primary medications of interest were beta blockers. Outcomes were modeled overall, accounting for the amount of exposure to the agent, and adjusting for baseline characteristics.

  Study phs001501

• Targeting FGFR1 for treatment of soft-tissue sarcoma (H021)

  Purpose: Altered FGFR1 signaling has emerged as therapeutic target in various epithelial malignancies. In contrast, the role of FGFR1 in soft-tissue sarcoma (STS) has not been established. Prompted by the detection and subsequent therapeutic inhibition of amplified FGFR1 in a patient with metastatic leiomyosarcoma, we investigated the oncogenic properties and potential as drug target of FGFR1 in STS.Experimental Design: The frequency of FGFR1 amplification and overexpression, as assessed by fluorescence in situ hybridization, microarray-based comparative genomic hybridization and mRNA expression profiling, SNP array profiling, and RNA sequencing, was determined in three independent patient cohorts. The sensitivity of STS cell lines with or without FGFR1 alterations to genetic and pharmacologic FGFR1 inhibition and the signaling pathways engaged by FGFR1 were investigated using short-term viability assays, long-term colony formation assays, and biochemical analysis.Results: Increased FGFR1 copy number was detected in 74 of 190 (38.9%; Cohort 1), 13 of 79 (16.5%; Cohort 2), and 80 of 254 (31.5%; Cohort 3) patients. FGFR1 overexpression occurred in 16 of 79 (20.2%, Cohort 2) and 39 of 254 (15.4%; Cohort 3) patients. Targeting of FGFR1 by short hairpin RNA-mediated knockdown and different small-molecule inhibitors (PD173074, AZD4547, BGJ398) revealed that the requirement for FGFR1 signaling in STS cells is primarily dictated by FGFR1 expression levels, and identified the MAPK-ERK1/2 axis as critical FGFR1 effector pathway.Conclusion: These data identify FGFR1 as driver gene in multiple STS subtypes and support FGFR1 inhibition, guided by patient selection according to FGFR1 expression and monitoring of MAPK-ERK1/2 signaling, as therapeutic option in this challenging group of diseases.H021

  Study EGAS00001001844

• RNAseq of 12q-amplified osteosarcomas

  RNA-seq of 12q-amplified osteosarcomas for detection of gene fusions and gene expression analysis. RNA-seq was used to look for novel gene fusions and promoter swapping events, and study the expression levels of identified 3' partners. Additionally, global gene expression patterns were used to separate cases into clusters.

  Study EGAS50000000494

• 13K T2D-GENES analysis files

  This data set includes the following summary level data files used for the 13k analysis of T2D-GENES data: wes.variants.list: list of variants to keep for any analysis of the exomes data wes.assoc.samples.list: list of samples to keep for association analysis wes.assoc.variants.list: list of variants to keep for association analysis wes.sv.assoc.txt: single variant association analysis results wes.gene.ptv.variants.list.txt: list of protein truncating variants to use in gene-level analysis wes.gene.ptv.assoc.txt: results from gene-level tests of protein truncating variants wes.gene.nsstrict.variants.list.txt: list of NSstrict variants to use in gene-level analysis wes.gene.nsstrict.assoc.txt: results from gene-level tests of NSstrict variants wes.gene.nsbroad.variants.list.txt: list of NSbroad variants to use in gene-level analysis wes.gene.nsbroad.assoc.txt: results from gene-level tests of NSbroad variants wes.gene.ns.variants.list.txt: list of non synonymous variants to use in gene-level analysis wes.gene.ns.assoc.txt: results from gene-level tests of non synonymous variants

  Dataset EGAD00010001188

• FHS-Net Social Networks

  Note: Data Use Restrictions: The data must only be used for genetic research projects solely in the area of health-related social-network research. This study compiles detailed information on family and social ties linked to participants in the offspring cohort of the Framingham Heart Study. The investigators took computerized information from self-report data used by the FHS for over 30 years to facilitate health exam scheduling. These tracking sheets asked participants to identify people close to them, which were assumed by the investigators to indicate a social tie. Individuals are listed as "egos" (if the ties are from their perspective) and/or "alters" (if they are linked as a friend or family members to one of the other participants). All egos were FHS offspring participants while alters could be FHS participants in any cohort or non-participants. This information was combined with internal FHS pedigree data on family ties to list family member alters (as well as the nature of their relationship). The resultant dataset therefore includes each ego-alter tie, the nature of their relationship and the start and end dates for their ties for each of seven waves for the offspring study. Due to privacy concerns, all exam dates for individuals are listed relative to the initial FHS exam date. The study investigators chose a random, confidential date, to which all initial exam dates are linked (by number of months from random date to initial exam date). With this information, researchers can have access to the temporal relationships among participants' exam dates while remaining unaware of the actual exam dates for individual participants. During each clinic exam cycle, the participants undergo a detailed examination including physical examination, medical history, laboratory testing, and electrocardiogram. Over the years, other tests (that may not be performed at every exam cycle) have included pulmonary function, lifestyle, physical function, cognitive function questionnaires, and various noninvasive cardiovascular tests including echocardiograms. This study involves phenotypic data from these exams including (when available) basic body measurements (height, weight, blood pressure), laboratory values (blood sugar levels, LDL levels), information on smoking and alcohol use, and tests of depression and cognitive functioning. Important links to apply for individual-level data Data Use Certification Requirements (DUC) Instructions to Request Authorized Access Apply here for controlled access to individual level data Participant Protection Policy FAQ In 1948, researchers recruited men and women from the town of Framingham, Massachusetts, beginning the first round of extensive physical examinations and lifestyle interviews that would later be analyzed for common patterns related to CVD development. Initially, the Framingham Heart Study enrolled 5,209 men and women from the Framingham area who were between the ages of 28 and 62 years. Beginning in 1971, the Framingham Heart Study enrolled 5,124 men and women, who were either offspring of the original cohort or spouses of those offspring. In 2002, 4,095 third generation participants (men and women) were enrolled.

  Study phs000153

• RNA Editing in breast cancer

  High-throughput sequencing screens suggest that RNA editing, which consists in the substitution of adenosine with inosine by the RNA-specific adenosine deaminase (ADAR) enzyme, occurs at several thousand positions across the human genome. Recent evidences have shown that RNA-editing could promote proliferation and carcinogenesis; however, the general principles of ADAR activity on the transcriptome and how ADAR is controlled in cancers remain to be established. The main aim of this project was to investigate the phenomenon of RNA editing in breast and other cancers. The frequency of A-to-I editing was evaluated in 58 breast cancers equally distributed among the different molecular subtypes and 10 normal breast tissues. The analysis was focused on defining: the relationship between the global amount of editing and ADAR expression; the ability to predict the level of editability of specific sites; the distribution of editing in normal and tumour samples and among different breast cancer subtypes; and the clinical, pathological and genomic factors affecting editing.

  Study EGAS00001000495