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• Alveolar Rhabdomyosarcoma case report

  Rhabdomyosarcoma (RMS) is a mesenchymal malignancy phenocopying muscle and is among the leading causes of death from childhood cancer. Metastatic alveolar rhabdomyosarcoma is the most aggressive subtype with an 8% five-year disease-free survival rate when a chromosomal fusion is present, and 40% five-year disease-free survival rate when negative for a fusion event. The underlying biology of PAX-fusion negative alveolar rhabdomyosarcoma remains largely unexplored and is exceedingly rare in Li-Fraumeni syndrome patients. Here, we present the case of an 11-year old male with fusion-negative alveolar rhabdomyosarcoma studied at end of life with a comprehensive functional genomics characterization, resulting in identification of potential therapeutic targets for broader investigation.

  Study EGAS00001004828

• GUARDIAN: The Insulin Resistance Atherosclerosis Family Study (IRASFS)

  TThe IRAS Family Study was a family study designed to examine the genetic and epidemiologic basis of glucose homeostasis traits and abdominal adiposity. Briefly, self-reported Mexican pedigrees were recruited in San Antonio, TX and San Luis Valley, CO. Probands with large families were recruited from the initial non-family-based IRAS Study, which was modestly enriched for impaired glucose tolerance and T2D. GUARDIAN includes 1,024 individuals in 88 pedigrees from the IRAS Family Study. Insulin sensitivity was obtained by FSIGT.

  Study phs001008

• Targeted DNA sequence

  Targeted DNA sequencing files that were used in our study. The cohort was composed of 36 cases of tumor-only targeted DNA sequencing data. All files are UMI processed. The panel is designed with Agilent Sure Select and the sequence was performed using DNBSEQ sequencer.

  Dataset EGAD50000000972

• Projects

  Projects Jointly managed by the European Bioinformatics Institute (EMBL-EBI) in Cambridge (UK) and the Centre for Genomic Regulation (CRG) in Barcelona, the EGA provides an invaluable service to the worldwide biomedical research community. The teams leading the EGA are involved in several international partnerships and consortia in numerous scientific fields, where they contribute to ambitious projects. In addition to the project listed below, the EGA is in a long-standing partnership with the Global Alliance for Genomics and Health (GA4GH), as described on the dedicated page. On-going projects Project Duration Domain Funder Tags CANDLE | CANDLE project aims to conceptualise and advance the development of National Cancer Data Nodes (NCDNs) in European countries. These NCDNs will boost the reuse of cancer data for research, innovation and policy making, in order to improve diagnostics and treatment for cancer patients, as well as prevention and early detection. 2025-2028 Cancer Horizon Europe DOCUMENTATION EASIGEN-DS | The EASIGEN-DS project aims to conduct a design study to establish a new European Research Infrastructure on Advanced Genomics Technologies, EASIGEN. To develop an excellent scientific, technological and operational design, we will conduct landscape studies, stakeholder consultations, and community surveying. 2025-2028 Genomic and health data Horizon Europe DATA MANAGEMENT DOCUMENTATION INFRASTRUCTURE Go-IMPaCT | Go-IMPaCT will contribute sequenced genomes and provide infrastructure as part of IMPaCT-Cohort, one of the three fundamental pillars of the Precision Medicine Infrastructure associated with Science and Technology (IMPaCT) program in Spain. Along with the Genome of Europe (GoE) project, around 18.000 people will have their genomes sequenced, also contributing to Spain's commitments in 1+MG. Go-IMPaCT will fund the development of an EGA node to manage and share this genomic and phenoclinic data, laying the foundations for regional and ethnic genomic variability in Spain to be available for research purposes. The IMPaCT cohort is created with the spirit of being an open research tool, compatible with the rest of the health research ecosystem, and other international initiatives. 2025-2027 Large-scale genomics and health data; personalised medicine Instituto de Salud Carlos III ACCESS DISCOVERY INFRASTRUCTURE METADATA STANDARDS FAIR-FEGA | This project seeks to accelerate data depositions into FEGA, significantly increasing the data flow in and from FEGA nodes. It will build capacity within the FEGA nodes and increase awareness in a wide range of stakeholders, thus altogether achieving the ultimate goal of enhancing data reuse. The project will be carried out by a strategic consortium comprising seven ELIXIR nodes and two ELIXIR communities. 2025-2026 Not applicable ELIXIR ACCESS DISCOVERY DOCUMENTATION INFRASTRUCTURE METADATA STANDARDS FEGA-Connect | A consortium of six ELIXIR nodes plus the Polish FEGA node (in-kind contribution) joining forces to build a solid base to develop solutions for effective multi-omic sensitive data integration between FEGA nodes and other infrastructures and specialised Data repositories. We aim to promote a more coherent data deposition, discoverability and retrieval of multi-omics datasets, providing FAIRer data and consequently accelerating research. 2025-2026 Multi-omics data ELIXIR ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE METADATA STANDARDS IMPaCT-Data 2 | IMPaCT-Data 2 will develop a digital platform for the integration and modelling of biomedical data associated with IMPaCT (Precision Medicine Infrastructure associated with Science and Technology) projects in Spain. It will deploy a sustainable infrastructure that facilitates the integration, standardisation, interoperability and analysis of clinical, genomic, molecular and medical imaging data. This platform will be aligned with European projects such as Genome of Europe (GoE), the first project to make use of the European Genomic Data Infrastructure (GDI), and EUCAIM. IMPaCT-Data 2 will benefit from advanced Artificial Intelligence and High Computing Capacity Systems capabilities, offering robust and accessible tools for researchers from the National Health System in Spain. 2025-2026 Large-scale genomics and health data; personalised medicine Instituto de Salud Carlos III ACCESS DISCOVERY INFRASTRUCTURE METADATA STANDARDS SenSec | This project aims to establish a mechanism for orchestrating secure access to sensitive data hosted by the EGA, whether in Central EGA or any Federated Node, from Galaxy, a popular open-source, community-driven VRE (Virtual Research Environment) for bioinformatics analysis. Building on a previous prototype that enabled Galaxy users within Trusted Research Environments (TREs) to decrypt sensitive data for workflow execution without sharing private encryption keys, SenSec will expand this prototype into a comprehensive solution for secure data analysis in Galaxy, facilitating encrypted data access and transfer from FEGA/EGA repositories to designated TREs. 2025-2026 Genomic and health data; trusted research environment ELIXIR ACCESS DATA ANALYSIS ERDERA | The European Rare Disease Research Alliance (ERDERA) takes over EJPRD to deliver concrete health benefits to rare disease patients in the next decade by advancing prevention, diagnosis and treatment research. To leave no one behind, over 170 organisations championed by the European Union and member states are working hand in hand to make Europe a world leader in rare diseases research and innovation. 2024-2034 Rare diseases Horizon Europe; "La Caixa" Foundation cofunds CRG's contribution ACCESS DATA ANALYSIS DISCOVERY INFRASTRUCTURE SYNTHIA | The aim of SYNTHIA is to deliver validated, reliable tools and methods for synthetic data generation (SDG). The tools will cover multiple data types including lab results, clinical notes, genomics, imaging and m-health data. SYNTHIA also hopes to make possible the generation of longitudinal data. 2024-2029 Genomic and health data; multi-omics; AI solutions Innovative Health Initiative (IHI) DATA ANALYSIS DATA MANAGEMENT INFRASTRUCTURE GoE | The Genome of Europe initiative aims to build a European network of national genomic reference cohorts of at least 500.000 citizens. These reference cohorts will be selected to be representative of the European population. 2024-2028 Large-scale genomic and health data Horizon Europe ACCESS DISCOVERY INFRASTRUCTURE METADATA STANDARDS HEREDITARY | HEREDITARY aims to transform the way we approach disease detection, prepare treatment response, and explore medical knowledge by building a robust, interoperable, trustworthy, and secure framework that integrates multimodal health data (including genetic data) while ensuring compliance with cross-national privacy-preserving policies. 2024-2027 Neurodegenerative disorders, gut-brain interplay Horizon Europe DATA MANAGEMENT DATA ANALYSIS EOSC-ENTRUST | The mission of EOSC-ENTRUST is to create a European network of trusted research environments for sensitive data and to drive European interoperability by joint development of a common blueprint for federated data access and analysis. 2024-2026 Trusted Research Environment Horizon Europe INFRASTRUCTURE EBV-MS | "Targeting Epstein-Barr Virus Infection for Treatment and Prevention of Multiple Sclerosis". The ambitious goals of the project are to answer the questions why only a few EBV infected persons develop MS, and define the underlying mechanism of this process, as well as clarify if targeting the EBV infection can prevent MS or improve the disease course. 2023-2028 Viral-host genetics; immune response; disease modelling; disease prevention; AI/ML solutions Horizon Europe DATA MANAGEMENT DATA ANALYSIS WISDOM | WELL-BEING IMPROVEMENT THROUGH THE INTEGRATION OF HEALTHCARE AND RESEARCH DATA AND MODELS WITHOUT BORDER FOR CHRONIC IMMUNE-MEDIATED DISEASES aims to deploy novel approaches for data processing, harmonisation, management, and secure data sharing and federated access for diseases like multiple sclerosis. Using an end-user guided approach, it will facilitate responsible and critical assessment of the use of AI in healthcare. 2023-2028 Chronic immune-mediated diseases Horizon Europe DATA MANAGEMENT INFRASTRUCTURE EUCAIM | EUropean Federation for CAncer IMages is a project that will build a highly secure, federated and large-scale European cancer imaging platform, with capabilities that will greatly enhance the potential of Artificial Intelligence in oncology. 2023-2027 Cancer Digital Europe Programme (DIGITAL) DISCOVERY CONTAGIO | CONTAGIO (COhorts Network To be Activated Globally In Outbreaks) aims to create coordination mechanisms to rapidly react to infectious disease (re-)emergence in low- and middle-income countries (LMICs). 2023-2026 Infectious Diseases European Commission - Horizon Europe ACCESS DATA MANAGEMENT DISCOVERY Youth-GEMs | Youth-GEMS (Gene Environment Interactions in Mental Health TrajectorieS of Youth) will conduct research into the genetic and environmental factors of mental health in young European people. 2022-2027 Mental health European Commission - Horizon Europe DATA MANAGEMENT DISCOVERY GDI | The European Genomics Data Infrastructure project is enabling access to genomic and related phenotypic and clinical data across Europe. It is doing this by establishing a federated, sustainable and secure infrastructure to access the data. 2022-2026 Genomic and health data European Commission - Horizon Europe; "La Caixa" Foundation cofunds CRG's contribution DISCOVERY DOCUMENTATION INFRASTRUCTURE IMPaCT-T2D | The IMPaCT-T2D project aims at studying the complete genomes of a large cohort of patients with Type 2 Diabetes mellitus (T2D), using modern sequencing technologies and artificial intelligence (AI) in order to improve the stratification and pharmacological treatment in the context of precision medicine. 2022-2025 Cardiovascular and Complex Diseases Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE Completed projects Project Duration Domain Funder Tags EOSC4Cancer | EOSC4Cancer builds on existing projects, research outcomes and established community solutions to create the federated FAIR data, analysis and services infrastructure needed for European Cancer research programmes. 2022-2025 Cancer European Commission - Horizon Europe DISCOVERY EuCanImage | A European Cancer Image Platform Linked to Biological and Health Data for Next-Generation Artificial Intelligence and Precision Medicine in Oncology. 2020-2025 AI Solutions in Oncology European Commission - H2020 Programme; "La Caixa" Foundation cofunds CRG's contribution DATA MANAGEMENT METADATA STANDARDS GenoMed4ALL | A consortium built to empower personalised medicine in the field of haematological diseases through the use of AI and the pooling of genomic and clinical data. 2020-2025 Hematological diseases European Commission - H2020 Programme DISCOVERY METADATA STANDARDS BY-COVID | The BeYond-COVID project aims to make COVID-19 data accessible to scientists in laboratories but also to anyone who can use it, such as medical staff in hospitals or government officials. Going beyond SARS-CoV-2 data, the project will provide a framework for making data from other infectious diseases open and accessible to everyone. 2021-2024 Infectious diseases European Commission - H2020 Programme ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE IMPaCT-Data | IMPaCT-Data aims to create the infrastructure for secondary use of data from Spanish healthcare systems - electronic health records, medical imaging and genomic repositories - and contribute with the knowledge and methodology produced to the healthcare system. 2021-2024 Large-scale genomics and health dataSpanish Ministry of Science and Innovation; Instituto de Salud Carlos III ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE LaMarato | It is a project aimed at creating and developing a catalan interhospitalary network to interrogate genetic variants from thousands of genetic tests carried out in patients with rare diseases from the main catalan hospitals. 2021-2024 Genomic and health data Fundacio La Marato de TV3 (catalan foundation) DISCOVERY HealthyCloud | This consortium will contribute a Strategic Agenda towards the European Health Research and Innovation Cloud. The project will work in collaboration with a broad range of stakeholders to ensure that all voices are included and that the results are technically and ethically sound. 2021-2023 Not Applicable European Commission - H2020 Programme DOCUMENTATION B1MG | Beyond 1 Million Genomes aims to create a network of genetic and clinical data across Europe. The project provides coordination and support to the 1+ Million Genomes Initiative (1+MG). This initiative is a commitment of 24 EU countries, the UK and Norway to give cross-border access to one million sequenced genomes by 2022. 2020-2023 Not applicable European Commission - Horizon Europe DATA MANAGEMENT INFRASTRUCTURE METADATA STANDARDS ELIXIR-CONVERGE | An alliance with the goal of Connecting and aligning ELIXIR Nodes to deliver sustainable FAIR life-science data management services. 2020-2023 Data Management and Infectious Diseases European Commission - H2020 Programme DATA MANAGEMENT INFRASTRUCTURE METADATA STANDARDS IHCC | The International HundredK+ Cohorts Consortium aims to create a global platform for translational research ? informing the biological and genetic basis for disease and improving clinical care and population health. 2020-2022 Translational research NIH; The Wellcome Trust; CZI INFRASTRUCTURE METADATA STANDARDS PPCG | The Pan Prostate Cancer Group aims to harmonise and interrogate Whole Genome DNA Sequence data generated around the world from over 2000 men with prostate cancer, with associated transcriptome and methylome data to include men from different clinical categories, and ethnicities. This project is about providing breakthrough advances through analysis of a very large series of Whole Genome DNA data from prostate cancer contributed by many of the leading scientists and clinicians working in prostate cancer genomics. 2019-2024 Cancer Cancer Research UK DATA MANAGEMENT CINECA | Consortium providing a Federated solution enabling population-scale genomic and biomolecular data accessible across international borders accelerating research and improving the health of individuals resident across continents. 2019-2023 Large-scale Genomics and Health Data European Commission - H2020 Programme ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE EASI-Genomics | A project designed to provide easy access to cutting-edge DNA sequencing technologies to researchers from academia and industry, within a framework that ensures compliance with ethical and legal requirements, as well as FAIR and secure data management. 2019-2023 Next Generation Sequencing European Commission - H2020 Programme ACCESS EJP-RD | An European consortium built to create a comprehensive, sustainable ecosystem allowing a virtuous circle between research, care, and medical innovation. 2019-2023 Rare diseases European Commission - H2020 Programme ACCESS DATA MANAGEMENT DOCUMENTATION METADATA STANDARDS EOSC-Life | EOSC-Life brings together the 13 Life Science research infrastructures (LS RIs) to create an open, digital and collaborative space for biological and medical research. The project will publish 'FAIR' data and a catalogue of services provided by participating RIs for the management, storage and reuse of data in the European Open Science Cloud (EOSC). 2019-2023 Not applicable European Commission - H2020 Programme DOCUMENTATION EUCANCan | A federated network aiming at implementing a cultural, technological and legal integrated framework across Europe and Canada, to enable and facilitate the efficient sharing of cancer genomic data. 2019-2023 Cancer European Commission - H2020 Programme DATA MANAGEMENT METADATA STANDARDS The Federated EGA framework: supporting sensitive data management across the ELIXIR Nodes | This project is a direct continuation of the FHD IS with the goal to position the FEGA framework as the core infrastructure driver to support human data sharing for research. 2019-2023 Human genomic data ELIXIR INFRASTRUCTURE UK Biobank | UK Biobank is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. This project is to archive whole genome sequencing and other genetic data for UK Biobank participants. 2019-2023 Large-scale Genomics and Health Data The Wellcome Trust; UKRI; Amgen; AstraZeneca; GSK; Johnson & Johnson DATA MANAGEMENT INFRASTRUCTURE VEIS | The core mission of VEIS is to create an open ecosystem of technologies that will address and adapt to the requirements of the systems used to analyse and interpret -omics and clinical data in research and application environments in biomedicine. The aim of the project is to leverage the value of the EGA for both industry and society. 2019-2022 Oncology and Rare diseases Generalitat de Catalunya and European Regional Development Fund (ERDF) ACCESS DISCOVERY ELIXIR BEACON IS | This study follows on from a number of earlier activities that have established the ELIXIR Beacon Project. The main aim is to extend the Beacon protocol, developed at EGA, to become the reference ELIXIR Data Discovery product 2019-2021 Not applicable ELIXIR DISCOVERY ELIXIR FHD IS | This project coordinates the delivery of FAIR compliant metadata standards, interfaces, and reference implementation to support the federated ELIXIR network of human data resources. 2019-2021 Human genomic data ELIXIR INFRASTRUCTURE ELIXIR Rare Disease | The Rare Disease Community extends and generalises the system of access authorisation and high volume secure data transfer developed within the EGA. The goal of the Community is to create a federated infrastructure that will enable researchers to discover, access and analyse different rare disease repositories across Europe. It is doing this in partnership with other European infrastructure projects, namely RD-CONNECT, BBMRI-ERIC and E-Rare.2019-2021 Rare diseases ELIXIR INFRASTRUCTURE Solve-RD | Solve-RD - solving the unsolved rare diseases - is a research project funded by the European Commission. It echoes the ambitious goals set out by the International Rare Diseases Research Consortium (IRDiRC) to deliver diagnostic tests for most rare diseases by 2020. The current diagnostic and subsequent therapeutic management of rare diseases is still highly unsatisfactory for a large proportion of rare disease patients - the unsolved RD cases. For these unsolved rare diseases, we are unable to explain the etiology responsible for the disease phenotype, predict the individual disease risk and/or rate of disease progression, and/or quantitate the risk of relatives to develop the same disorder. 2018-2024 Rare diseases European Commission - H2020 Programme ACCESS DATA MANAGEMENT METADATA STANDARDS EuCanShare | An EU-Canada joint infrastructure for next-generation multi-Study Heart research. 2018-2022 Cardiovascular Diseases European Commission - H2020 Programme ACCESS METADATA STANDARDS

  Documentation about/projects-and-funders/projects

• Patient-derived conditionally reprogrammed cells (CRCs) were established and characterized to assess their biological properties and to apply these to test the efficacies of drugs.

  RNA seq data was used for the characterization and profiling of the created patient-derived cells and in vivo tissue.

  Study EGAS00001001702

• Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN Study)

  This research study focuses on the genomic and psychological environmental effects on blood pressure among mothers and their children. The study includes 250 mothers who self-identify as AA/black, and 250 children between the ages of 3 and 5 years old at the time of enrollment. The study is longitudinal and data collection interviews are scheduled every six months for two years after enrollment, for a total of four participant interviews. Assessment is as follows: genetic (time 1 only) and psychological factors (every six months for two years).

  Study phs001792

• Leucocyte eQTLs in autoimmune disease and health

  Peripheral blood was taken from healthy controls and patients with active autoimmune disease. CD4 T cells, CD8 T cells, monocytes, neutrophils, and B cells were separated using magnetic-activated cell sorting. RNA and genomic DNA was extracted from cell lysates using Qiagen Allprep kits. Genotyping of healthy controls and patients with inflammatory bowel disease was performed using the Illumina Human OmniExpress12v1.0 BeadChip at the Wellcome Trust Sanger Institute. 200 ng RNA was processed for hybridization onto Affymetrix Human Gene ST 1.1 microarrays. Gene expression and genotyping data was used to perform eQTL mapping.

  Study EGAS00001001251

• IκBε deficiency accelerates disease development in chronic lymphocytic leukemia

  The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-κB activity and disease expansion. We found that IκBε loss leads to NF-κB pathway activation and promotes both migration and proliferation of CLL cells in a dose-dependent manner. Importantly, NFKBIE inactivation was sufficient to induce a more rapid expansion of the CLL clone in lymphoid organs and contributed to the development of an aggressive disease with a shortened survival in both xenografts and genetically modified mice. IκBε deficiency was associated with an alteration of the MAPK pathway, also confirmed by RNA-sequencing in NFKBIE-mutated patient samples, and resistance to the BTK inhibitor ibrutinib. In summary, our work underscores the multimodal relevance of the NF-κB pathway in CLL and paves the way to translate these findings into novel therapeutic options.

  Dataset EGAD50000000754

• M116 Proteome Extracellular Vesicle Profiling

  For extracellular vesicles (ECV) extraction from plasma, 1M ammonium acetate was added to precipitate ECVs on ice for 45 min. Then, 100 mM ammonium acetate was added to the mixture, and ECVs were precipitated by centrifugation at 20,000g for 30 min. ECVs were washed with 50 mM ammonium bicarbonate (Sigma-Aldrich, Cat. 1066-33-7). Then, 600 µl of 1% ammonium deoxycholate (Sigma Aldrich, Cat. K2755-1MG) were added. The concentration of protein in each sample was measured using a bicinchoninic acid assay (BCA assay). Ammonium bicarbonate was used to dilute 500 µg of protein into a final volume of 500 µl. Next, dithiothreitol (Sigma-Aldrich, Cat. D9779) was added to obtain a final concentration of 20 mM, followed by iodoacetamide (Sigma-Aldrich, Cat. I6125) to a final concentration of 40 mM. Next, trypsin (Roche, Cat. RTRYP-RO) was added to the sample in a 1:25 protein ratio and incubated at 37°C overnight. Next day, formic acid (ThermoFisher Scientific, Cat. 28905) in a final concentration of 0.1% was added and extraction of proteins was done using Empore™ Solid Phase Extraction Cartridges (3M), following manufacturer’s instructions. The eluted samples were then centrifuged for 90 min. using a speed vacuum centrifuge (Thermo, RC1010), followed by snap freezing in liquid nitrogen. Then, the samples were kept in a freeze dryer (LyoDry Compact Benchtop, MechaTech) overnight. Next, the samples were reconstituted in 30 µl of 0.1% formic acid (FA) and an o-Phthaladehyde (Oparil) assay was performed to determine the concentration of each sample. After that, the sample was prepared in a concentration of 0.5 µg/µl using 0.1% FA and alcohol dehydrogenase (ADH). The samples were prepared in glass mass spectrometry vials for proteomic analysis using a Waters Synapt G2Si High-Definition Mass Spectrometry (Waters Corporation) operated by the MassLynx 4.1., 110 min. running time with 2 µl of an injection containing 1 µg of peptide. Quality controls were also run along with samples to guarantee consistency. Pooled quality controls were made from all samples, in which the samples were run at the beginning, middle and end of the mass spectrometry run. Samples were randomized before running the experiment. The proteomic data was then imported into Progenesis software 4.2 (Nonlinear Dynamic, UK) to identify and quantify peptides and proteins.

  Dataset EGAD50000001679

• Ghana Breast Health Study

  The Ghana Breast Health Study (GBHS) was a multi-disciplinary, population-based case-control study conducted in Accra and Kumasi, Ghana that was designed to investigate breast cancer etiology in the West Africa region. The study enrolled 1,126 invasive breast cancer cases and 2,106 frequency matched population-based controls using census-based sampling. GHBS participants were between the ages of 18 to 74 years of age. Breast cancer cases were recruited at the time they presented with lesions suspicious of breast cancer at three hospitals: Korle Bu Teaching Hospital (Accra), Komfo Anoyke Teaching Hospital (Kumasi) and Peace and Love Hospital (Kumasi). These hospitals are the primary providers of treatment for breast cancer in Ghana, allowing for cases in our study to represent most breast cancers diagnosed in these areas during the study period. The following publications describe the GBHS in detail: 1) Brinton LA et al. Design considerations for identifying breast cancer risk factors in a population-based study in Africa. Int J Cancer 2017;140:2667-2677 (PMID:28295287). 2) Nyante SJ et al. Recruiting population controls for case-control studies in sub-Saharan Africa: The Ghana Breast Health Study. PloS one 2019;14:e0215347 (PMID:30990841)Among subjects with an available source of germline DNA genotyping was performed using the Infinium Global Screening Array-24 per the manufacturer’s guidelines using the Infinium automated protocol. We excluded probable duplicates and close relatives, and samples with a call rate < 95% or samples with extreme heterozygosity. Female sex was verified by Identifiler using X chromosome heterozygosity and the X chromosome inbreeding coefficient F statistics. The GLU genetics’ ld.tagzilla module was used to confirm African ancestry. To resolve more detailed population substructure, principal components analysis was conducted among all unrelated subjects using the EIGENSOFT v7.2.1. Imputation was performed using the Michigan imputation server Minimac3 with 1K genomes phase3 as reference panel.

  Study phs002387