Decoding Genetics, Ancestry, and Geospatial Context for Precision Health

Satoshi Koyama; Ying Wang; Kaavya Paruchuri; Md Mesbah Uddin; So Mi J Cho; Sarah M Urbut; Sara Haidermota; Whitney E Hornsby; Robert C Green; Mark J Daly; Benjamin M Neale; Patrick T Ellinor; Jordan W Smoller; Matthew S Lebo; Elizabeth W Karlson; Alicia R Martin; Pradeep Natarajan

doi:10.1101/2023.10.24.23297096

Decoding Genetics, Ancestry, and Geospatial Context for Precision Health

medRxiv [Preprint]. 2023 Oct 25:2023.10.24.23297096. doi: 10.1101/2023.10.24.23297096.

Authors

Satoshi Koyama^{1

2

3}, Ying Wang^{1

4

5}, Kaavya Paruchuri^{1

2

3}, Md Mesbah Uddin^{1

2}, So Mi J Cho^{1

2

6}, Sarah M Urbut^{1

2}, Sara Haidermota^{1

2}, Whitney E Hornsby^{1

2}, Robert C Green^{3

7

8}, Mark J Daly^{4

5

9

10}, Benjamin M Neale^{1

4

5}, Patrick T Ellinor^{1

2

3}, Jordan W Smoller^{3

11

12}, Matthew S Lebo^{3

13

14}, Elizabeth W Karlson^{3

13

15}, Alicia R Martin^{1

4

5}, Pradeep Natarajan^{1

2

3}

Affiliations

¹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
² Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁷ Department of Medicine (Genetics), MassGeneralBrigham, Boston, MA, USA.
⁸ Broad Institute and Ariadne Labs, Boston, MA, USA.
⁹ Institute for Molecular Medicine Finland (FIMM), Finland.
¹⁰ University of Helsinki, Helsinki, Finland.
¹¹ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹² Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹³ Mass General Brigham Personalized Medicine, Cambridge, MA, USA.
¹⁴ Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
¹⁵ Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital., Boston, MA, USA.

Abstract

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), encompassing 142,238 participants, to unravel the intricate relationships among genomic profiles, environmental context, and disease manifestations within clinical practice. In this study, we highlight the impact of ancestral diversity in the MGBB by employing population genetics, geospatial assessment, and association analyses of rare and common genetic variants. The population structures captured by the genetics mirror the sequential immigration to the Greater Boston area throughout American history, highlighting communities tied to shared genetic and environmental factors. 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.

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Abstract

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