437 results for "《云南省人民政府办公厅关于印发云南省省级信息化项目管理办法的通知》（云政办发〔2024〕21号）"

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• INCLUDE: The Epidemiology of Transient Leukemia in Newborns with Down Syndrome

  The INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project is an NIH-wide collaboration that seeks to improve health and quality-of-life for people with Down syndrome. The INCLUDE Project Data Coordinating Center and partners created the INCLUDE Data Hub, a centralized data resource that allows access to large-scale clinical and multi-omics datasets specific to Down syndrome and supports collaborative, cloud-based analysis to accelerate scientific discoveries related to Down syndrome and its co-occurring conditions.Down syndrome (DS) is associated with a remarkably high risk of childhood acute myeloid leukemia (AML), with an approximately 500-fold increased risk of the rare subtype acute megakaryoblastic leukemia. Though largely treatable, a proportion of myeloid leukemia in DS (ML-DS) patients relapse with dismal survival. ML-DS is preceded by a preleukemia, transient abnormal myelopoiesis (TAM), which presents clinically at birth and is driven by somatic truncating mutations in the erythro-megakaryocytic transcription factor gene GATA1. Up to 15% of DS newborns have TAM, and this can be fatal in up to 20% of cases. A further 10-15% of newborns with DS harbor subclonal GATA1 mutations with clinically silent disease (i.e., Silent TAM). Of the DS newborns with either TAM or Silent TAM (i.e., transient leukemia), up to 15% will acquire additional somatic mutations and progress to ML-DS. We predict that germline variation modifies the risk of developing somatic truncating GATA1 mutations, the first step towards ML-DS, however this has yet to be examined. To address this, the main aim of this X01 study is to perform the first genetic association study of GATA1 mutations in DS, through whole-genome sequencing (WGS) of 470 DS newborns in the Oxford Down Syndrome Cohort Study (ODSCS). Targeted sequencing of GATA1 has already been performed in the 470 DS newborns in the ODSCS, with 130 (28%) confirmed to harbor a somatic truncating GATA1 mutation. We will perform a genome-wide association study (GWAS) of GATA1 mutations to assess genetic variation genome-wide, in particular focusing on variants in candidate genes on the trisomic chromosome 21, RUNX1, ERG, ETS2, and DYRK1A, which have previously been associated with upregulation of GATA1. We will also carry out a chromosome X-wide association study (XWAS) to investigate genetic variation at the GATA1 gene, which resides on chromosome X. WGS data will also enable us to assess the potential role of copy number variation in the risk of transient leukemia in DS. Discovering genetic risk factors for GATA1 mutations in DS may reveal targets for new targeted therapies for TAM, and also inform the etiology of ML-DS as well as AML in the non-DS population. Finally, the ODSCS includes rich phenotypic data for the 470 DS newborns, including clinical diagnosis of TAM and other hematologic complications, complete blood counts, maternal pregnancy complications, and information on congenital heart disease and other birth defects. Thus, whole genome sequencing data in DS newborns from the ODSCS will provide a rich resource for the DS research community.

  Study phs002982

• RNA Expression in Diverse Donor Derived Dermal Fibroblasts Correlates with Reprogramming to Pluripotency

  The cohort used in this study includes 36 African American (17 female, 19 male) and 36 White American (19 female, 17 male) individuals. The total cohort has a median age of 32 years, with a range of 20-64 years. The African American cohort has a median age of 34, with a range of 21-52 years. The White American cohort has a median age of 31, with a range of 20-64 years. Primary dermal fibroblast lines were derived from skin biopsies obtained from adult individuals at the NIEHS under institutional review board approved protocol human subjects 10-E-0063, "Sample Collection Registry for Quality Control of Biological and Environmental Specimens and Assay Development and Testing protocol" (ClinicalTrials.gov #NCT01087307). All participants gave written informed consent for tissue donation. Donor sex, age, and ancestry were voluntarily self-reported. Fibroblast cells were reprogrammed via lentiviral transduction using six transcription factors contained in three plasmids (ADDGENE/PSIN4-EF2-N2L, ADDGENE/PSIN4-EF2-O2S and ADDGENE/PSIN4-CMV-K2M). Reprogramming efficiency was determined by alkaline phosphatase staining of triplicate 10cm reprogrammed dishes containing colonies, which were then scanned. The saved images were analyzed with ImageJ 1.51h (Wayne Rasband, National Institutes of Health, USA) to count colonies, using color threshold adjusted and binary converted images of each dish. Triplicate plates were averaged and reported as colony counts or percent reprogramming efficiency ((# of colonies/250,000) x100). The African American cohort had reprogramming efficiencies ranging from 0.06-1.37%, with a median of 0.655%. The White American cohort had reprogramming efficiencies ranging from 0.02-1.13%, with a median of 0.455%. Our goal was to define transcriptomic heterogeneity that could be contributing to differences in reprogramming efficiency between individuals and between groups. Total RNA was obtained from dermal fibroblasts and matched iPSCs. For each sample, 500 ng total RNA was used as input for preparation of whole transcriptome rRNA depleted libraries. An adapter-ligated library was prepared with the KAPA HyperPrep Kit (KAPA Biosystems, Wilmington, MA) using Bioo Scientific NEXTflex™ DNA Barcoded Adapters (Bioo Scientific, Austin, TX, USA) according to KAPA-provided protocol. Sequencing was performed using an Illumina HiSeq 2500 following Illumina-provided protocols for 2x150 bp paired-end sequencing. Each transcriptome was sequenced to a target depth of 125 million reads. The following mean raw reads were obtained: African American dermal fibroblasts= 129,571,450; White American dermal fibroblasts= 131,939,505; African American iPSCs= 132,501,335; White American iPSCs= 134,394,164. Raw reads were aligned to hg19 using the STAR alignment tool (https://github.com/alexdobin/STAR). The following mean aligned reads were obtained: African American dermal fibroblasts= 123,315,343; White American dermal fibroblasts= 125,178,035; African American iPSCs= 123,148,312; White American iPSCs= 123,886,992. Reprinted from L. C. Mackey et al., Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming. Stem Cells 36, 1697-1708 (2018), with permission from Wiley. Reprinted from L. S. Bisogno et al., Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes. Science Advances 6 (47) (2020) (PMID: 33219026), with permission from AAAS.

  Study phs002341

• ALCHEMIST Study

  The ALCHEMIST study will accrue patients that are potentially eligible for the Intergroup adjuvant studies and perform central EGFR and ALK genotyping using a central reference laboratory certified by the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Patients may either present prior to surgery with resectable NSCLC, may present following complete resection (before or after adjuvant chemotherapy). Eligibility is limited to those with NSCLC of a non-squamous histological subtype and those with adequate performance status and organ function for future trial eligibility. All subjects must submit tissue for central EGFR and ALK genotyping, as well as additional tissue for advanced genomics at the CCG. Subjects may have had local genotyping done prior to registration, however if these results shows no targetable EGFR or ALK alterations (or if it shows a KRAS mutation) then the patient will not be eligible for this screening protocol given the primary aim is to facilitate accrual to the adjuvant studies. All subjects will provide peripheral blood for matched normal DNA. All subjects (including those known to have EGFR or ALK alterations with local genotyping) will have formalin-fixed tissue collected for central genotyping. The testing will be performed at Response Genetics (Los Angeles, CA), a commercial CLIA-certified laboratory. ALK FISH will be performed using the Vysis break-apart probe and EGFR sequencing will be performed of exons 18-21. It is preferred that a full tumor block be submitted, but if unavailable, 15 unstained slides can be submitted. Genotyping results are expected to be provided to the treating clinician within 14 business days of submission so they can be used to determine eligibility for the randomized adjuvant studies, or to confirm the local results. Results will also be reported at intervals to the study team for update into the Alliance database. In addition to the commercial genotyping at Response Genetics, tissue will be collected for research genomics by CCG. For those patients with a block available, this will be forwarded to the CCG after clinical testing at Response Genetics. For patients without a block available, 15 unstained slides should be submitted to the CCG BCR for exploratory analysis. A peripheral blood specimen will also be collected and sent to the CCG BCR to use as matched normal. Specimens will be coded. Over the course of the study, the CCG will perform advanced genomic analysis of the resected lung cancer specimens in a research, non-CLIA environment. Following completion of the genomic analysis, the results can be matched with the clinical follow-up results using a link between the samples codes and the patient identifiers for correlative analyses. Subjects participating in the follow-up portion of the ALCHEMIST study, as well as those participating in the adjuvant therapeutic studies, are expected to undergo a standard-of-care diagnostic biopsy to confirm recurrence. At least two core biopsies, minimum, should be obtained as part of this recurrence biopsy. Paraffin embedded tissue from this biopsy will be used for confirmation of recurrence, for CLIA genomics to plan subsequent clinical trials, and for additional research genomics by the CCG. Plasma will additionally be collected at recurrence and sent to CCG for study of circulating free DNA (cfDNA). Data for the ALCHEMIST study is not yet available to be accessed by the public at this time; when ready it will be made available at the GDC Data Portal.

  Study phs001140

• ARDSNet 07-08: Randomized, Blinded, Placebo-Controlled, Multi-Center Trial of Omega-3 Fatty Acid, Gamma-Linolenic Acid, and Antioxidants in Acute Lung Injury or ARDS (OMEGA) (ARDSNet-Omega-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from ARDSNet-Omega include bronchial lavage, plasma, urine, and DNA. Please note that use of biospecimens in genetic research is subject to a tiered consent.Objectives: To determine if dietary supplementation of omega-3 (n-3) fatty acids, γ-linolenic acid and antioxidants to participants with acute lung injury would increase ventilator-free days to study day 28.Background: Early acute lung injury (ALI) is characterized by neutrophilic lung inflammation, permeability, and intravascular and alveolar fibrin deposition. The type and inflammatory activity of eicosanoids liberated during inflammation depends on the membrane phospholipid composition: omega 6 (n-6) fatty acid arachidonate yields highly reactive and inflammatory dienoic prostaglandins and series 4 leukotrienes, whereas omega-3 (n-3) fatty acids favor production of less active and potentially anti-inflammatory trienoic prostaglandins and series 5 leukotrienes. Participants at risk of developing ALI have n-3 levels approximately 25% of normal and those with established ALI have n-3 levels as low as 6% of normal, suggesting a potential role for n-3 dietary supplementation in participants with ALI.Three randomized controlled studies, conducted in participants with ALI or sepsis-induced respiratory failure, demonstrated an association between the administration of an enteral formula enriched in n-3 fatty acids, GLA, and antioxidants and improved oxygenation and respiratory physiology compared with an unenriched, high-fat formula. However, interpretation of these results is limited by the small sample sizes and as-treated analyses of only those participants who tolerated full enteral nutrition. Participants: The total number of participants in the study was 272.Design: Participants were stratified by hospital and the presence of shock at baseline and then randomized to receive either twice-daily enteral supplementation of n-3 fatty acids, GLA, and antioxidants (n-3 supplement) or an isocaloric-isovolemic carbohydrate-rich control. Participants were also simultaneously randomized to a separate ongoing trial (the EDEN study) comparing low- vs full-calorie enteral nutrition in a 2×2 factorial design.The n-3 or control supplement was administered enterally as twice-daily boluses of 120 mL beginning within 6 hours of randomization. Dosing continued until the earliest of 21 days, 48 hours of unassisted breathing, or extubation. The energy provided by the boluses supplemented that provided by each primary physician's choice of standard continuous non–n-3-enriched enteral formula. The rate of continuous enteral feeding was managed by a protocol with an algorithm for gastrointestinal intolerances. The supplement was administered even if enteral nutrition was interrupted, as long as the patient was tolerating enteral medications. Conclusions: The study was stopped by the DSMB for futility at the first interim analysis after 143 participants had been randomized to receive the n-3 supplement and 129 to receive the isocaloric control. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, participants receiving the n-3 supplement had fewer ventilator-free days, intensive care unit–free days, and nonpulmonary organ failure-free days.

  Study phs003744

• Modifier Genes in 21-hydroxylase Deficiency

  CAH is a genetic steroidogenesis disorder. The most common form, 21OHD, leads to cortisol deficiency and, in turn, an excess of androgen, a hormone that promotes the development and maintenance of male sex characteristics. As a result of this androgen excess, prepubescent males and newborn, prepubescent, and grown females exhibit mature masculine characteristics. The symptoms and severity of 21OHD vary among individuals with the disease and in adults versus children. The reasons for these differences are not yet known. Current therapy for 21OHD consists of administration of glucocorticoids to replace cortisol and suppress excessive pituitary function. With more information about what genes or factors contribute to the severity of 21OHD, researchers may be able to better treat children and adults with the disease. This study will examine participants' DNA to determine what other genes may affect the severity of 21OHD and may make the disease milder in adults than in children This is a 3-day inpatient study. Once eligibility is confirmed through physical exam and blood analysis, eligible participants are admitted to the study site in the morning on the first study day. A blood sample is taken and participants receive one 10-mg pill of hydrocortisone. Heart rates and blood pressures are taken every 4 hours throughout the day. In the morning of Day 2, a blood sample will be obtained and a 24 hour urine collection will begin. On the morning of Day 3, another blood sample is obtained. Participants then receive intravenous cosyntropin, a synthetic form of a hormone that the body makes. About 1 hour after this, participants provide a final blood sample. Participants receive a pill of hydrocortisone prior to the end of the study.

  Study phs001313

• Federated EGA

  Federated EGA Federated EGA Index Overview Map of FEGA status across the world Current status of the FEGA Network Documentation Overview Federated EGA is a global network of repositories enabling secure discovery and access to sensitive human data. Our vision is to accelerate scientific discovery and healthcare breakthroughs by creating the go-to worldwide sensitive human data resource. Our values are: Privacy & Trust: Ensuring privacy of data subjects, security of services and acting with integrity to build community trust.FAIRness: Driving reuse of data through standardisation of metadata and clear access policies.Diversity: Expanding our network and representing global diversity in the data we host to bring benefits worldwide. Federated EGA - European by name, global by nature Federated EGA collaborates with European and global initiatives (GA4GH, ELIXIR, 1+ Million Genomes Framework, GDI), demonstrating that a network for transnational discovery of and access to human data is possible. By providing a solution to emerging challenges around secure and efficient management of human omics and associated data, the FEGA Network fosters data reuse, enables reproducibility, and accelerates biomedical research. For general enquiries or to request more information about Federated EGA, please reach out to us here. Read more about the Federated EGA in our commentary in Nature Genetics! Learn more about setting up a Federated EGA Node in our onboarding documentation. Map of FEGA status across the world Current status of the FEGA Network Node Description Joined CEGA Central EGA is managed by the Centre for Genomic Regulation (CRG) and EMBL-EBI. The EGA has been a trusted repository for sensitive data since 2008. CEGA coordinates the FEGA network, hosts central services and the EGA catalogue. 2022 Finland FEGA Finland is hosted by CSC - IT Center for Science Ltd., which is the national ELIXIR Node in Finland. CSC is a state-owned company specialising in providing high-quality IT infrastructure and services for Finnish higher education and research. 2022 Germany The German Human Genome-Phenome archive (GHGA) is part of the German National Research Data Infrastructure (NFDI). It is coordinated by the German Cancer Research Center (DKFZ) and includes over 20 academic partners. 2022 Norway FEGA Norway is a service by ELIXIR Norway, the Norwegian node of the European organisation ELIXIR. University of Oslo as a partner institution in ELIXIR Norway is hosting the service relying on the TSD infrastructure for sensitive data. ELIXIR Norway is a consortium of 5 Norwegian universities and is coordinated by University of Bergen. 2022 Spain FEGA Spain is co-hosted by the Barcelona Supercomputer Center (BSC) and the Centre for Genomic Regulation (CRG), both part of ELIXIR Spain and the Spanish National Infrastructure for Personalised Medicine associated with Science and Technology (IMPaCT). 2022 Sweden FEGA Sweden is hosted by the National Bioinformatics Infrastructure Sweden (NBIS), which legally is part of Uppsala University. NBIS forms the bioinformatics platform at SciLifeLab and constitutes the Swedish node of the European organisation ELIXIR. 2022 Poland FEGA Poland is hosted by Biobank Lodz, which is part of University of Lodz. Biobank Lodz is an element of the infrastructure of the Regional Digital Medicine Centers established by the Medical Research Agency. 2022 Portugal FEGA Portugal is managed by BioData.pt, the distributed infrastructure for Life and Health data for Portugal. This entity is a non-profit association of 15 life sciences R&I organisations spread across the country, and the home of ELIXIR Node in Portugal. 2023 Canada Canadian Genome-phenome Archive is part of the Pan Canadian Genome Library, with the mandate to allow the secure and responsible sharing and analysis of Canadian genomic information. 2024 Switzerland Swiss FEGA is hosted by SIB Swiss Institute of Bioinformatics, which is the national ELIXIR Node in Switzerland, on behalf of the Swiss FEGA Partnership which includes 4 other key partners (ETH Zurich, Health 2030 Genome Center, Swiss Data Science Center and Switch). 2025 Documentation Title Version Description Mission, vision, values Federated EGA Mission, vision, values 1.0 The official Mission-Vision-Values statement for FEGA, produced and formally approved by the FEGA Strategic Committee in September 2025. Structure and Organisation Federated EGA Structure and Organisation 1.1 New version under review, coming January 2026. Strategic Committee Federated EGA Strategic Committee 1.1 Terms of reference for the FEGA Strategic Committee describe the purpose and objectives of the committee, which is to provide direction and strategic planning for the FEGA network. The committee receives input from, and provides feedback for the EGA Strategic Committee. Operations Committee Federated EGA Operations Committee 1.1 Terms of reference for the FEGA Operations Committee describe the purpose and objectives of the committee, which is to review operational performance and coordinate technical roadmaps of FEGA Nodes and Central EGA. The committee receives advice from, and provides operational reporting to the FEGA Strategic Committee. Guidelines Node Operations guidelines 2.1 An overview of the operational areas which require resources in order to create a FEGA Node. The document is based on more than 15 years' experience of EMBL-EBI and CRG operating the EGA and initial expericences of the inaugural FEGA Nodes. The operational areas of responsability are in line with the FEGA Maturity Model, which guides establishment and operation of FEGA Nodes. Collaboration Federated EGA Node Collaboration Agreement 1.3 Nodes are welcome to make a copy of this current version of the CA to start its review with their legal teams and understand the responsibilities of joining FEGA. Nevertheless, this version (the one with a watermark) shall not be signed: the official version needs to be obtained from FEGA prior signing through its official channels.

  Documentation about/projects-and-funders/federated-ega

• NHLBI TOPMed - NHGRI CCDG: The BioMe Biobank at Mount Sinai

  The IPM BioMe Biobank, founded in September 2007, is an ongoing, broadly-consented electronic health record (EHR)-linked clinical care biobank that enrolls participants non-selectively from the Mount Sinai Medical Center patient population. BioMe currently comprises >42,000 participants from diverse ancestries, characterized by a broad spectrum of longitudinal biomedical traits. Participants are enrolled through an opt-in process and consent to be followed throughout their clinical care (past, present, and future) in real-time, allowing us to integrate their genomic information with their EHRs for discovery research and clinical care implementation. BioMe participants consent for recall, based on their genotype and/or phenotype, permitting in-depth follow-up and functional studies for selected participants at any time. Phenotypic and genomic data are stored in a secure database and made available to investigators, contingent on approval by the BioMe Governing Board. BioMe uses a "data-broker" system to protect confidentiality. Ancestral diversity - BioMe participants represent a broad racial, ethnic and socioeconomic diversity with a distinct and population-specific disease burden. Specifically, BioMe participants are of African (AA), Hispanic/Latino (HL), European (EA) and other/mixed ancestry. BioMe participants are predominantly of African (AA, 24%), Hispanic/Latino (HL, 35%), European (EA, 32%), and other ancestry (OA, 10%). Participants who self-identify as Hispanic/Latino further report to be of Puerto Rican (39%), Dominican (23%), Central/South American (17%), Mexican (5%) or other Hispanic (16%) ancestry. More than 40% of European ancestry participants are genetically determined to be of Ashkenazi Jewish ancestry. With this broad ancestral diversity, BioMe is uniquely positioned to examine the impact of demographic and evolutionary forces that have shaped common disease risk. Phenotypes available in BioMe - BioMe has a high-quality and validated set of fully implemented clinical phenotype data that has been culled by a multi-disciplinary team of experienced investigators, clinicians, information technologists, data-managers, and programmers who apply advanced medical informatics and data mining tools to extract and harmonize EHRs. BioMe, as a cohort, offers a great versatility for designing nested case-control sample-sets, particularly for studying longitudinal traits and co-morbidity in disease burden. Biomedical and clinical outcomes: The BioMe Biobank is linked to Mount Sinai's system-wide Epic EHR, which captures a full spectrum of biomedical phenotypes, including clinical outcomes, covariate and exposure data from past, present and future health care encounters. As such, the BioMe Biobank has a longitudinal design as participants consent to make all of their EHR data from past (dating back as far as 2003), present and future inpatient or outpatient encounters available for research, without restriction. The median number of outpatient encounters is 21 per participant, reflecting predominant enrollment of participants with common chronic conditions from primary care facilities. Environmental data: The clinical and EHR information is complemented by detailed demographic and lifestyle information, including ancestry, residence history, country of origin, personal and familial medical history, education, socio-economic status, physical activity, smoking, dietary habits, alcohol intake, and body weight history, which is collected in a systematic manner by interview-based questionnaire at time of enrollment. The IPM BioMe Biobank contributed ~10,600 DNA samples for whole genome sequencing to the TOPMed program. Samples were selected for the Coronary Artery Disease (CAD) and the Chronic Obstructive Pulmonary Disease (COPD) working groups. Using a Case-Definition-Algorithm (CDA), we identified ~4,100 individuals with CAD (~50% women) and ~3,000 individuals as controls (65% women). In addition, we identified ~800 individuals with COPD (62% women) and 1800 individuals as controls (72% women). Another 600 BioMe participants with Atrial Fibrillation, all of African ancestry, were included.

  Study phs001644

• Bogalusa Heart Study (BHS-BioLINCC)

  Objectives: To investigate the early natural history of cardiovascular disease in a cohort of children and young adults in a biracial, semirural community.Background: The Bogalusa Heart Study has been a long-term epidemiologic study. The investigators have identified and followed black and white participants for nearly 40 years, and have described the incidence and prevalence of biologic and behavioral cardiovascular disease risk factors from childhood through adulthood. Their participation has enabled the study to not only document differences between males and females, but also between blacks and whites. The results from the Bogalusa Heart Study have clearly documented that the genesis of atherosclerosis has its basis in childhood, and that prevention can and must begin at the early ages.The Bogalusa Heart Study had been funded over the years by the Specialized Centers of Research (SCOR) Program. The SCOR program was initiated by NHLBI in 1970 to expedite the development and application of new knowledge essential for improved diagnosis, treatment, and prevention of arteriosclerosis, hypertension, pulmonary disease, and thrombosis. In 1984 a Demonstration and Education Component was added to the parent SCOR of the Bogalusa Heart Study in order to translate the experience gained in epidemiological studies into an intervention study designed to retard the development of cardiovascular risk factors in children. Beginning in 1997, the study was supported by the cooperative agreement mechanism. Participants: The Bogalusa dataset includes 11,796 participants that attended at least one of seven cross-sectional pediatric exams and/or the 1995-96 adult examination. Subjects ranged in age from 3 to 20 years at the pediatric exams and 20-37 at the time of the adult exam. Approximately 6,000 have more than one examination constituting a dynamic cohort. Design: The initial survey in 1973-1974 was restricted to children ages 2 1/2 to 14. A physical examination was conducted and information was collected on anthropometric data, hemoglobin, blood pressure, serum lipids, and health history. Over 3,500 children participated. The second cross-sectional survey of 1976-1977 and subsequent surveys expanded the eligible population to include all children ages 5-17 years. The second survey of over 4,000 children also included information on salt intake, smoking, health beliefs, and attitudes, and for girls ages 8-17, menstrual history and oral contraceptive use. The third survey of over 3,500 participants in 1978-1979 also collected anthropometric measurements on skinfold thickness and two measurements of heart rate. The fourth survey of over 3,300 participants in 1981-1982 added data on alcohol use, Type A behavior, peer networks and dieting habits.The Bogalusa Heart Study continued to use a cross-sectional and longitudinal design with the general cross-sectional survey of approximately 3,700 Bogalusa children ages five to seventeen in 1988-1989 in the sixth screen and additional longitudinal studies to recall children in defined subgroups for more intensive evaluation. Half of the 12,000 participants screened since 1973 had been studied three or more times. The Post High School Study examined young adults ages 21 through 30 who previously were examined as children ages five through fourteen in the first Bogalusa Heart Study screening in 1973-1974. The population included approximately 4,603 young adults originally screened and any other children or adolescents examined for the first time in any subsequent surveys. The cardiovascular phenotypes include obesity, blood pressure, lipids, lipoproteins, apoproteins, homocysteine, glucose-insulin, fibrinogen, plasminogen activator inhibitor-1 and von Willebrand Factor. Environmental risk factors consist of sociodemographic characteristics, tobacco and alcohol use, oral contraception, physical activity, cognitive and physical function, and quality of sleep and diet. Subclinical morbidity includes echo-Doppler measurements of cardiac-carotid structure and function.

  Study phs004173

• Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

  Human Induced Pluripotent Stem Cells (hiPSC) are an established patient-specific model system where opportunities are emerging for cell-based therapies. We compared and contrasted hiPSCs derived from different tissues, skin and blood, in the same individual. We show extensive single-nucleotide mutagenesis in all hiPSC lines, although fibroblast-derived hiPSCs (F-hiPSCs) are particularly heavily mutagenized by ultraviolet (UV)-related damage. We utilized genome sequencing data on 454 F-hiPSCs and 44 blood-derived hiPSCs (B-hiPSCs) to gain further insights. Across 324 whole genome sequenced (WGS) F-hiPSCs derived by the Human Induced Pluripotent Stem Cell Initiative (HipSci), UV-related damage is present in ~72% of cell lines, sometimes causing substantial mutagenesis (range 0.25-15 per Mb). Furthermore, we find remarkable genomic heterogeneity between independent F-hiPSC clones derived from the same reprogramming process in the same donor, due to oligoclonal populations within fibroblasts. Combining WGS and exome-sequencing data of 452 HipSci F-hiPSCs, we identify 272 predicted pathogenic mutations in cancer-related genes, of which 21 genes were hit recurrently three or more times, involving 77 (17%) lines. Notably, 151 of 272 mutations were present in starting fibroblast populations suggesting that more than half of putative driver events in F-hiPSCs were acquired in vivo. In contrast, B-hiPSCs reprogrammed from erythroblasts show lower levels of genome-wide mutations (range 0.28-1.4 per Mb), no UV damage, but a strikingly high prevalence of acquired BCOR mutations in ~57% of lines, indicative of strong selection pressure. All hiPSCs had otherwise stable, diploid genomes on karyotypic pre-screening, highlighting how copy-number-based approaches do not have the required resolution to detect widespread nucleotide mutagenesis. This work strongly suggests that models for cell-based therapies require detailed nucleotide-resolution characterization prior to clinical application.

  Dataset EGAD00001007029

• The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium Study

  The AMBER Consortium Study was formed to pool interview data, questionnaire data, and biological samples from epidemiological studies of breast cancer in African-American women to discover the potential causes of early-onset and aggressive breast cancer in African-American women. AMBER is funded through a Program Project grant from the National Cancer Institute. Genetic data submitted to dbGaP come from participants in the Carolina Breast Cancer Study, Women's Circle of Health Study, and Black Women's Health Study. The P01 consists of four scientific projects; the aims include follow-up on previous GWAS findings for breast cancer susceptibility in AA women as well as investigation of SNPs in candidate genes in biologically plausible pathways. These SNPs were genotyped using DNA from 3130 African-American women with breast cancer and 3700 controls. Descriptions of the original studies that provided the data and samples for this collaborative study are given below. The Carolina Breast Cancer Study (CBCS): a North Carolina population-based case-control study of breast cancer, conducted in three phases. The current study phase, phase 3 (years 2008-2014), includes women residents in 44 counties. CBCS phases 1 and 2 were conducted in 24 counties. Breast cancer cases are identified using Rapid Case Ascertainment in cooperation with the NC Central Cancer Registry. Controls were identified for phases 1 and 2 only (1993-1996 and 1996-2001), using Division of Motor Vehicles lists for women under age 65 and Health Care Financing Administration lists for women 65 and older. Randomized recruitment was used to oversample AA women and women under age 50. In-depth interviews are conducted by study nurses in participants' homes to obtain information on potential risk factors for breast cancer. DNA samples have been obtained from most participants. Overall response rates for Phases 1 and 2 were 74% for AA cases and 54% for AA controls. Phase 3, conducted in 44 counties from 2008-2014, includes cases only. The response rate for AA cases in Phase 3 was 70.5%. The Women's Circle of Health Study (WCHS): a multi-site case-control study in New York City (NYC) and New Jersey (NJ) aimed at evaluating risk factors for early and aggressive breast cancer in women of AA and EA ancestry. Recruitment in NYC took place between January 2002 and December 2008 and involved hospital-based ascertainment of cases, while controls were identified through random digit dialing (RDD). Recruitment at the NJ site started in March 2006 and is ongoing. Phase I of the study ended in April 2012 and covered seven counties in NJ. WCHS2 includes two additional counties. Cases in NJ were identified from 2006 to 2012 by the NJ State Cancer Registry using rapid case ascertainment. Controls were initially recruited though RDD (2006 to 2010) and later through community-based efforts (2009-2012). In-person interviews ascertained data on established and suspected risk factors for breast cancer. DNA samples were obtained. Among eligible AA women, 75% in NY and 54% in NJ completed an interview and provided a biologic specimen. Black Women's Health Study (BWHS): an ongoing prospective cohort study of health and illness among U.S. black women, with a focus on cancer. The study began in 1995 when 59,000 AA women 21-69 years of age from across the United States completed a 14-page postal health questionnaire. The median age at entry was 38, and participants were residents of 17 states in mainland U.S.: Northeast, 28%; South, 30%; Midwest, 23%; West, 19%. The baseline questionnaire elicited information on a wide range of variables, including demographic factors, use of medical care, family history of breast cancer, reproductive and medical history, cigarette and alcohol use, weight, height, waist and hip circumference, medication use, diet, and exercise. Biennial follow-up questionnaires ascertain new cases of breast cancer and other illnesses and update covariate information. Medical record and cancer registry data are sought for all participants who report a diagnosis of breast cancer. As of 2014, approximately 80% of the baseline cohort have completed follow-up. DNA samples were obtained from about 50% of participants. BWHS data for the AMBER consortium were prepared as a nested case-control study, with controls frequency-matched to cases on year of birth, geographic region, and most recent questionnaire completed prior to the end of the at-risk period.

  Study phs000669