Genetics and context for precision health in Greater Boston
Mass General Brigham, an integrated healthcare system based in the Greater Boston area of Massachusetts, annually serves 1.5 million patients. We established the Mass General Brigham Biobank (MGBB), currently encompassing 142,238 participants, to unravel the intricate relationships among genomic profiles, environmental context, and disease manifestations within clinical practice. In this manuscript, we described genetic and phenotypic diversity and their interaction in the MGBB by employing population genetics, geospatial assessment, and association analyses of rare and common genetic variants. The population genetic variation captured the demographic histories in the Greater Boston area throughout American history, highlighting communities tied to shared genetic and environmental factors. Furthermore, our phenome-wide association analysis with socioeconomic factors, as well as common and rare genetic variants, prioritized disease causes across a tertiary academic medical center and community-based health system. Our investigation underscores the potency of unbiased, large-scale analyses in a healthcare-affiliated biobank, elucidating the dynamic interplay across genetics, immigration, structural geospatial factors, and health outcomes in one of the earliest American sites of European colonization.
Authors
- Md Mesbah Uddin (ORCID: https://orcid.org/0000-0003-1846-0411)
- Satoshi Koyama (ORCID: https://orcid.org/0000-0002-9286-0360)
- Benjamin M. Neale (ORCID: https://orcid.org/0000-0003-1513-6077)
- Himani Kamineni (ORCID: https://orcid.org/0009-0005-0863-5064)
- Sara Haidermota (ORCID: https://orcid.org/0000-0002-8588-3388)
- Jordan W. Smoller (ORCID: https://orcid.org/0000-0002-0381-6334)
- Pradeep Natarajan (ORCID: https://orcid.org/0000-0001-8402-7435)
- Susan A. Slaugenhaupt (ORCID: https://orcid.org/0000-0002-1658-5213)
- Alicia R. Martin (ORCID: https://orcid.org/0000-0003-0241-3522)
- Sarah Urbut (ORCID: https://orcid.org/0000-0002-1135-9647)
- Kaavya Paruchuri (ORCID: https://orcid.org/0000-0003-1228-1674)
- So Mi Jemma Cho (ORCID: https://orcid.org/0000-0003-2460-3335)
- Patrick T. Ellinor (ORCID: https://orcid.org/0000-0002-2067-0533)
- Akl C. Fahed (ORCID: https://orcid.org/0000-0002-4849-6389)
- Ying Wang (ORCID: https://orcid.org/0000-0001-7808-6279)
- Matthew S. Lebo (ORCID: https://orcid.org/0000-0002-9733-5207)
- Whitney Hornsby (ORCID: https://orcid.org/0000-0002-0672-0338)
- Yang Sui
- Robert C. Green (ORCID: https://orcid.org/0000-0001-8472-0424)
- Mark J. Daly (ORCID: https://orcid.org/0000-0002-0949-8752)
- Elizabeth W Karlson
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- University of Helsinki (FI)
- Harvard University (US)
- Yonsei University (KR)
- Massachusetts General Hospital (US)
- Institute for Molecular Medicine Finland (FI)
- Center for Systems Biology (US)
- Ariadne Diagnostics (United States) (US)
- Mass General Brigham (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1038/s41467-025-66598-8
- Citations
- 3
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 5.45