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

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, Freeze 8 (GRCh38) and Freeze 9b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 8, Phases 1-4" and "TOPMed Whole Genome Sequencing Project - Freeze 9b, Phases 1-4". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

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 Weblinks:
  • The Charles Bronfman Institute for Personalized Medicine
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Cohort
  • Genotype
  • Sequencing
• dbGaP estimated ancestry using GRAF-pop
• Subject Sample Telemetry Report (SSTR)

BioMe participants are enrolled non-selectively from the Mount Sinai Medical Center patient population. For the TOPMed Program, only adult (>18 yrs) participants, who had been diagnosed with COPD and/or CAD (cases) and/or Atrial Fibrillation, and who did not have a diagnosis of COPD and CAD (controls), were selected for sequencing.

• 2007: IPM BioMe Biobank started recruitment at the Mount Sinai Medical Center.
• 2010 December: Almost 3,000 BioMe participants (Africa, European and Hispanic ancestry) were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0.
• 2011 August: IPM BioMe Biobank joined the eMERGE II Network.
• 2012 November: A total of 23,000 participants had been recruited.
• 2012 December: An additional ~13,000 BioMe participants were genotyped using the Illumina HumanOmniExpress BeadChip and the ExomeChip.
• 2013 June: IPM BioMe Biobank joined the PAGE II Network.
• 2016 June: 10,000 BioMe participants had been genotyped using Illumina MEGA Platform. As such, around 20,000 unique BioMe participants had genome-wide genotyping data (including Exomchip).
• 2017 January: IPM BioMe Biobank joined the TOPMed Program.
• 2018 Summer: DNA of ~10,600 BioMe participants had been WGS sequenced.

• Primary Phenotype: Coronary Artery Disease
• Pulmonary Disease, Chronic Obstructive
• Atrial Fibrillation

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• PMC

• Principal Investigators
  • Ruth Loos, PhD. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Eimear Kenny, PhD. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• BioMe Director
  • Judy Cho, MD. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• Funding Sources
  • The Andrea and Charles Bronfman Philanthropies. Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • U01HG006380. National Institutes of Health, Bethesda, MD, USA.
  • U01HG007417. National Institutes of Health, Bethesda, MD, USA.
  • X01HL134588. National Institutes of Health, Bethesda, MD, USA.