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Clinical MedicineIn-Press PreviewGeneticsImmunology Open Access | 10.1172/JCI181802

Proteogenomic analysis integrated with electronic health records data reveals disease-associated variants in Black Americans

Usman A. Tahir,1 Jacob L. Barber,1 Daniel E. Cruz,1 Meltem Ece Kars,2 Shuliang Deng,1 Bjoernar Tuftin,2 Madeline G. Gillman,3 Mark D. Benson,1 Jeremy M. Robbins,1 Zsu-Zsu Chen,1 Prashant Rao,1 Daniel H. Katz,4 Laurie Farrell,1 Tamar Sofer,1 Michael E. Hall,5 Lynette Ekunwe,5 Russell P. Tracy,6 Peter Durda,6 Kent D. Taylor,7 Yongmei Liu,8 W. Craig Johnson,9 Xiuqing Guo,7 Yii-Der Ida Chen,7 Ani W. Manichaikul,10 Deepti Jain,11 Thomas J. Wang,12 Alex P. Reiner,11 Pradeep Natarajan,13 Yuval Itan,3 Stephen S. Rich,10 Jerome I. Rotter,7 James G. Wilson,1 Laura M. Raffield,3 and Robert E. Gerszten1

1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

Find articles by Tahir, U. in: JCI | PubMed | Google Scholar |

1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

Find articles by Deng, S. in: JCI | PubMed | Google Scholar |

1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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1Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States of America

2Mount Sinai School of Medicine, New York, United States of America

3University of North Carolina School of Medicine, Raleigh, United States of America

4Stanford University School of Medicine, Stanford, United States of America

5University of Mississippi Medical Center, Jackson, United States of America

6Department of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, United States of America

7The Institute for Translational Genomics and Population Sciences, Departmen, The Lundquist Institute for Biomedical Innovation, Torrance, United States of America

8Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States of America

9Department of Biostatistics, University of Washington, Seattle, United States of America

10Center for Public Health Genomics, University of Virginia, Charlottesville, United States of America

11University of Washington, Seattle, United States of America

12Department of Medicine, UT Southwestern Medical Center, Dallas, United States of America

13Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America

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Published September 24, 2024 - More info

J Clin Invest. https://doi.org/10.1172/JCI181802.
Copyright © 2024, Tahir et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 24, 2024 - Version history
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Abstract

BACKGROUND. Most genome wide association studies (GWAS) of plasma proteomics have focused on White individuals of European ancestry, limiting biological insight from other ancestry enriched protein quantitative loci (pQTL).

METHODS. We conducted a discovery GWAS of ~3,000 plasma proteins measured by the antibody based Olink platform in 1,054 Black adults from the Jackson Heart Study (JHS), and validated our findings in the Multi-Ethnic Study of Atherosclerosis (MESA). The genetic architecture of identified pQTLs were further explored through fine mapping and admixture association analysis. Finally, using our pQTL findings, we performed a phenome wide association study (PheWAS) across two large multi-ethnic electronic health record (EHR) systems in All of Us and BioMe.

RESULTS. We identified 1002 pQTLs for 925 proteins. Fine mapping and admixture analyses suggested allelic heterogeneity of the plasma proteome across diverse populations. We identified associations for variants enriched in African ancestry, many in diseases that lack precise biomarkers, including cis-pQTLs for Cathepsin L (CTSL) and Siglec-9 that were linked with sarcoidosis and non-Hodgkin’s lymphoma, respectively. We found concordant associations across clinical diagnoses and laboratory measurements, elucidating disease pathways, including a cis-pQTL associated with circulating CD58, white blood cell count, and multiple sclerosis.

CONCLUSIONS. Our findings emphasize the value of leveraging diverse populations to enhance biological insights from proteomics GWAS, and we have made this resource readily available as an interactive web portal.

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