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• UK Biobank whole cohort directly genotyped and imputed data (~500,000 participants)

  Genotype data is available for all 500,000 participants in the UK Biobank cohort. Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants and the remaining 450,000 participants have been genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content).Quality control and imputation (to over 90 million SNPs, indels and large structural variants) has been performed by a collaborative group headed by the Wellcome Trust Centre for Human Genetics.The following data are available:* A clean set of QC’ed genotype calls* Confidence values that a genotype call is correct* Intensity data to generate cluster plots* Extensive QC information regarding SNPs and samples including SNP metrics, batch effects, population structure and relatedness* Imputed dataFor further information, please refer to the UK Biobank website

  Study EGAS00001002399

• Whole Genome Association Study of Bipolar Disorder

  The goal of the project is to identify genes that make individuals more susceptible to bipolar disorder (manic depressive illness) and to better understand the brain pathways involved in the disease. Dataset versioning Version 1: European-American (EA) ancestry only Version 2: Version 1 plus African-American (AA) ancestry Version 3: EA and AA samples plus updated diagnostic criteria Consent groups and participant set General research use (GRU): 1767 controls (1081 EA controls, 686 AA controls) This consent group includes all controls for the Bipolar study, which are a subset of controls for the Schizophrenia study (subset of Schizophrenia: GRU). Bipolar and related disorders (BARD): 841 cases (691 EA cases, 150 AA cases) This consent group includes a subset of the Bipolar cases. Bipolar disorder only (BDO): 653 cases (388 EA cases, 265 AA cases) This consent group includes a subset of the Bipolar cases.

  Study phs000017

• Center for Common Disease Genomics [CCDG] - Cardiovascular ATVB: Atherosclerosis Thrombosis and Vascular Biology

  Italian Atherosclerosis Thrombosis and Vascular Biology study is a prospective, nationwide, case-control study involving 125 coronary care units in Italy. The cases were patients who were hospitalised for a first MI before the age of 45 years and underwent coronary angiography. Acute MI was defined as resting chest pain lasting more than 30 minutes, accompanied by persistent electrocardiographic changes, and confirmed by an increase in total creatine kinase or in the MB fraction to more than twice the upper normal limits. The controls were healthy subjects without a history of thromboembolic disease who were unrelated to the patients, but individually matched with them by age, gender and geographical origin. They were enrolled from among the blood donors or staff of the same participating hospitals. Recruitment of cases and controls took place between 1994 and 2007. This site hosts data from ~60 whole exomes.

  Study phs001592

• HuBMAP: KULMAP - Human Kidney, Urinary Tract, and Lung Mapping Center

  The major goal of the Human Kidney, Urinary Tract, and Lung Mapping Center (KULMAP) is to generate multi-omic and spatially resolved molecular anatomical maps of the human bladder, ureter and kidneys (BUKMAP) and the lung airways and parenchyma (LAPMAP) at a single cell resolution. This entails sequencing of the transcriptomes and epigenomes of dissociated single cells in a massively parallel manner. These profiles will then inform on highly multiplexed RNA in situ imaging for spatial mapping of hundreds of molecular targets in the tissue sections, at a subcellular resolution. These spatial molecular maps will serve as scaffolds for computational registration of cell types and the associated transcriptome/chromatin maps to the tissue space. The combination of sequencing single dissociated cells and multiplexed in situ mapping will allow the construction of detailed spatial maps for these large organs.

  Study phs002249

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): NIH Digital Health Solutions for COVID-19: IBM Covid19 Contact Tracing and Data Exchange Tools

  The goal of this project is to develop both contact tracing and secure data exchange tools. The contact tracing solution securely combines data from a variety of sources (including manual self-report data and mobile device surveys) to enable tracing of contacts with individuals that have tested positive for COVID-19 or have been exposed to COVID-19. The data exchange solution is a secure mechanism that empowers users to control the data they share in the course of their return to work, including the ability to provide a verifiable health status claim. These tools are being used by an employer to evaluate the risk of allowing individuals to return to normal activities, and also the ability to trace user contact with individuals diagnosed with or suspected of having contracted COVID-19. DOI: https://rapids.ll.mit.edu/10.57895/h0an-m559

  Study phs002516

• Breast Cancer Susceptibility

  Genetic factors account for a large fraction of breast cancer risk and it is estimated that up to 30% of breast cancers have a heritable component. Inherited cancer susceptibility is associated with early-onset of malignancies in general. Although 20% of young women with breast cancer have germline mutations in the best understood breast cancer susceptibility genes, BRCA1, BRCA2 and TP53, in the remaining 80% of women with early-onset breast cancer, the genetic factors contributing to disease remain unexplained. By studying the extreme phenotype of women diagnosed at an early age there is enrichment for genetic factors that contribute to breast cancer. This study contains the whole exome sequence of 384 women diagnosed with invasive breast cancer prior to 40 years of age. Each of the subjects reported a family history of breast cancer and lacked mutations in BRCA1 and BRCA2.

  Study phs001017

• Deciphering Maternal-Fetal Crosstalk in the Human Placenta During Parturition Using Single-Cell RNA-Sequencing

  Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal crosstalk in labor have not been fully elucidated. In this latest version (#5), scRNA-seq was applied to decipher maternal-fetal signaling in the human placenta and chorioamniotic membranes during term labor. Samples were obtained from women who underwent spontaneous labor (n = 24) or who were delivered in the absence of spontaneous labor (n = 18) at term. Samples from previous versions (#1-3) of this study include the placental villous tree, basal plate, and chorioamniotic membranes of women across a range of pregnancy physiologic and pathologic conditions, including the processes of labor (term labor and preterm labor), and COVID-19 (version #3). Version #4 includes samples from the human myometrium during spontaneous term labor.

  Study phs001886

• Study of Adaptation to Hypoxia in Ethiopian Highlanders via Whole Genome Sequencing

  Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome (either exons or a subset of SNPs) or a group of candidate genes, interpretation of the results was limited. We focused our study on Ethiopian highlander populations, which have been found to be well adapted to high altitudes (~3500m). We sequenced and analyze the genomes of 13 high altitude native Ethiopians: 6 individuals of Oromo heritage living on Bale Plateau (labeled "Oromos"), and 7 individuals residing on the Chennek field in the Simien Mountains (labeled "Amhara"). Our study revealed evolutionarily conserved genes that modulate hypoxia tolerance.

  Study phs000647

• Genome-Wide Analysis of Splenic Marginal Zone Lymphoma

  Splenic Marginal Zone Lymphoma (SMZL) is a B-cell malignancy of unknown pathogenesis and thus orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis of 8 paired tumor-normal DNAs from patients with SMZL, we show that the typical SMZL exome carries ~30 genetic alterations. Targeted resequencing of selected candidates in an extended panel of 40-117 samples revealed activating mutations of NOTCH2, a gene required for marginal-zone (MZ) development, as the most frequent and SMZL-specific lesion, accounting for approximately 20% of cases. Additional altered genes suggest that deregulation of signaling pathways normally involved in MZ development (NOTCH, NF-kappa B, and B-cell receptor) represents a critical event in SMZL pathogenesis. These findings have direct implications for the treatment of SMZL patients since drugs are available which can target NOTCH as well as other pathways deregulated in this disease.

  Study phs000502

• DAXX restoration suppresses alternative lengthening of telomeres in ATRX wild-type cells

  Many tumors maintain chromosome ends through a telomerase-independent, homologous recombination based mechanism called alternative lengthening of telomeres (ALT). While ALT occurs in only a subset of tumors, it is strongly associated with mutations in the genes encoding components of the histone H3.3 chaperone complex, ATRX and DAXX. To date the mechanistic role of ATRX and particularly DAXX mutations in potentiating ALT remains poorly understood. We identify an osteosarcoma cell line, G292, with a unique chromosomal translocation resulting in loss of DAXX function, while retaining functional ATRX. Using this distinctive resource, we demonstrate that introduction of wild type DAXX suppresses the ALT phenotype and restores localization of the ATRX/DAXX complex to PML bodies. This provides the first direct molecular evidence that ongoing DAXX deficiency is essential for maintenance of the ALT phenotype and highlights the potential for therapeutic targeting of this oncogenic pathway.

  Study phs001495