Machine learning models for predicting blood pressure phenotypes by combining multiple polygenic risk scores.

Journal: Scientific reports
PMID: 38816422

Abstract

We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic and clinical variables and polygenic risk scores (PRSs). We developed a two-model ensemble, consisting of a baseline model, where prediction is based on demographic and clinical variables only, and a genetic model, where we also include PRSs. We evaluate the use of a linear versus a non-linear model at both the baseline and the genetic model levels and assess the improvement in performance when incorporating multiple PRSs. We report the ensemble model's performance as percentage variance explained (PVE) on a held-out test dataset. A non-linear baseline model improved the PVEs from 28.1 to 30.1% (SBP) and 14.3% to 17.4% (DBP) compared with a linear baseline model. Including seven PRSs in the genetic model computed based on the largest available GWAS of SBP/DBP improved the genetic model PVE from 4.8 to 5.1% (SBP) and 4.7 to 5% (DBP) compared to using a single PRS. Adding additional 14 PRSs computed based on two independent GWASs further increased the genetic model PVE to 6.3% (SBP) and 5.7% (DBP). PVE differed across self-reported race/ethnicity groups, with primarily all non-White groups benefitting from the inclusion of additional PRSs. In summary, non-linear ML models improves BP prediction in models incorporating diverse populations.

Authors

  • Yana Hrytsenko
    Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Benjamin Shea
    CardioVascular Institute (CVI), Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Michael Elgart
    Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA. melgart@bwh.harvard.edu.
  • Nuzulul Kurniansyah
    Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Genevieve Lyons
    XY Health, Cambridge, MA, United States.
  • Alanna C Morrison
    Department of Epidemiology, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • April P Carson
    Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Bernhard Haring
    Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Braxton D Mitchell
    Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Bruce M Psaty
    Department of Medicine, University of Washington, Seattle, WA, USA.
  • Byron C Jaeger
    Kirklin Institute for Research in Surgical Outcomes, University of Alabama at Birmingham.
  • C Charles Gu
    The Center for Biostatistics and Data Science, Washington University, St. Louis, USA.
  • Charles Kooperberg
    Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Daniel Levy
    The Framingham Heart Study, Framingham, MA 01701, USA.
  • Donald Lloyd-Jones
    Feinberg School of Medicine, Northwestern University, Chicago, IL, U.S.A.
  • Eunhee Choi
    Department of Internal Medicine, Lincoln Medical Center, Bronx, NY, United States.
  • Jennifer A Brody
    Department of Medicine, University of Washington, Seattle, WA, USA.
  • Jennifer A Smith
    Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Jerome I Rotter
    Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Matthew Moll
    Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.
  • Myriam Fornage
    Department of Epidemiology, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Noah Simon
    Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
  • Peter Castaldi
    Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Ramon Casanova
    Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
  • Ren-Hua Chung
    Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
  • Robert Kaplan
    Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Ruth J F Loos
    The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Sharon L R Kardia
    Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Stephen S Rich
    Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Susan Redline
    Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard University Boston, MA.
  • Tanika Kelly
    Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
  • Timothy O'Connor
  • Wei Zhao
    Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, Jiangnan University, Wuxi 214122, Jiangsu Province, P. R. China. lxy@jiangnan.edu.cn zhuye@jiangnan.edu.cn.
  • Wonji Kim
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, USA.
  • Xiuqing Guo
    Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Yii-Der Ida Chen
    Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Tamar Sofer
    Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.

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