Frontiers in Neuroscience (Jun 2021)
Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis
- Jennifer A. Sumner,
- Adam X. Maihofer,
- Adam X. Maihofer,
- Vasiliki Michopoulos,
- Vasiliki Michopoulos,
- Alex O. Rothbaum,
- Lynn M. Almli,
- Ole A. Andreassen,
- Ole A. Andreassen,
- Allison E. Ashley-Koch,
- Dewleen G. Baker,
- Dewleen G. Baker,
- Jean C. Beckham,
- Jean C. Beckham,
- Jean C. Beckham,
- Bekh Bradley,
- Bekh Bradley,
- Gerome Breen,
- Gerome Breen,
- Jonathan R. I. Coleman,
- Jonathan R. I. Coleman,
- Anders M. Dale,
- Anders M. Dale,
- Michelle F. Dennis,
- Michelle F. Dennis,
- Michelle F. Dennis,
- Norah C. Feeny,
- Carol E. Franz,
- Melanie E. Garrett,
- Charles F. Gillespie,
- Guia Guffanti,
- Guia Guffanti,
- Michael A. Hauser,
- Sian M. J. Hemmings,
- Sian M. J. Hemmings,
- Tanja Jovanovic,
- Nathan A. Kimbrel,
- Nathan A. Kimbrel,
- Nathan A. Kimbrel,
- William S. Kremen,
- William S. Kremen,
- Bruce R. Lawford,
- Mark W. Logue,
- Mark W. Logue,
- Mark W. Logue,
- Mark W. Logue,
- Adriana Lori,
- Michael J. Lyons,
- Jessica Maples-Keller,
- Matig R. Mavissakalian,
- Regina E. McGlinchey,
- Divya Mehta,
- Rebecca Mellor,
- William Milberg,
- Mark W. Miller,
- Mark W. Miller,
- Charles Phillip Morris,
- Matthew S. Panizzon,
- Kerry J. Ressler,
- Kerry J. Ressler,
- Kerry J. Ressler,
- Victoria B. Risbrough,
- Victoria B. Risbrough,
- Barbara O. Rothbaum,
- Peter Roy-Byrne,
- Soraya Seedat,
- Soraya Seedat,
- Alicia K. Smith,
- Alicia K. Smith,
- Jennifer S. Stevens,
- Leigh Luella van den Heuvel,
- Leigh Luella van den Heuvel,
- Joanne Voisey,
- Joanne Voisey,
- Ross McD Young,
- Lori A. Zoellner,
- Caroline M. Nievergelt,
- Caroline M. Nievergelt,
- Erika J. Wolf,
- Erika J. Wolf
Affiliations
- Jennifer A. Sumner
- Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States
- Adam X. Maihofer
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- Adam X. Maihofer
- Veterans Affairs San Diego Healthcare System, VA Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, United States
- Vasiliki Michopoulos
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Vasiliki Michopoulos
- Yerkes National Primate Research Center, Atlanta, GA, United States
- Alex O. Rothbaum
- Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, United States
- Lynn M. Almli
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, United States
- Ole A. Andreassen
- NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Ole A. Andreassen
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Allison E. Ashley-Koch
- 0Duke Molecular Physiology Institute, Duke University, Durham, NC, United States
- Dewleen G. Baker
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- Dewleen G. Baker
- Veterans Affairs San Diego Healthcare System, VA Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, United States
- Jean C. Beckham
- 1Durham VA Health Care System, Durham, NC, United States
- Jean C. Beckham
- 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
- Jean C. Beckham
- 3VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC), Genetics Research Laboratory, Durham, NC, United States
- Bekh Bradley
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Bekh Bradley
- 4Atlanta VA Health Care System, Decatur, GA, United States
- Gerome Breen
- 5Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
- Gerome Breen
- 6NIHR BRC at the Maudsley, King’s College London, London, United Kingdom
- Jonathan R. I. Coleman
- 5Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
- Jonathan R. I. Coleman
- 6NIHR BRC at the Maudsley, King’s College London, London, United Kingdom
- Anders M. Dale
- 7Department of Radiology, University of California, San Diego, San Diego, CA, United States
- Anders M. Dale
- 8Department of Neurosciences, University of California, San Diego, San Diego, CA, United States
- Michelle F. Dennis
- 1Durham VA Health Care System, Durham, NC, United States
- Michelle F. Dennis
- 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
- Michelle F. Dennis
- 3VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC), Genetics Research Laboratory, Durham, NC, United States
- Norah C. Feeny
- Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, United States
- Carol E. Franz
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- Melanie E. Garrett
- 0Duke Molecular Physiology Institute, Duke University, Durham, NC, United States
- Charles F. Gillespie
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Guia Guffanti
- 9Department of Psychiatry, Harvard Medical School, Boston, MA, United States
- Guia Guffanti
- 0McLean Hospital, Belmont, MA, United States
- Michael A. Hauser
- 0Duke Molecular Physiology Institute, Duke University, Durham, NC, United States
- Sian M. J. Hemmings
- 1Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Sian M. J. Hemmings
- 2South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa
- Tanja Jovanovic
- 3Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, United States
- Nathan A. Kimbrel
- 1Durham VA Health Care System, Durham, NC, United States
- Nathan A. Kimbrel
- 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States
- Nathan A. Kimbrel
- 3VA Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC), Genetics Research Laboratory, Durham, NC, United States
- William S. Kremen
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- William S. Kremen
- Veterans Affairs San Diego Healthcare System, VA Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, United States
- Bruce R. Lawford
- 4School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia
- Mark W. Logue
- 5National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States
- Mark W. Logue
- 6Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States
- Mark W. Logue
- 7Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
- Mark W. Logue
- 8Biomedical Genetics, Boston University School of Medicine, Boston, MA, United States
- Adriana Lori
- 9Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, United States
- Michael J. Lyons
- 0Department of Psychological & Brain Sciences, Boston University, Boston, MA, United States
- Jessica Maples-Keller
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Matig R. Mavissakalian
- 1Department of Psychiatry, Case Western Reserve University, Cleveland, OH, United States
- Regina E. McGlinchey
- 2GRECC/TRACTS, VA Boston Healthcare System, Boston, MA, United States
- Divya Mehta
- 3Center for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD, Australia
- Rebecca Mellor
- 4Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, QLD, Australia
- William Milberg
- 2GRECC/TRACTS, VA Boston Healthcare System, Boston, MA, United States
- Mark W. Miller
- 5National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States
- Mark W. Miller
- 6Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States
- Charles Phillip Morris
- 4School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia
- Matthew S. Panizzon
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- Kerry J. Ressler
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Kerry J. Ressler
- 9Department of Psychiatry, Harvard Medical School, Boston, MA, United States
- Kerry J. Ressler
- 0McLean Hospital, Belmont, MA, United States
- Victoria B. Risbrough
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- Victoria B. Risbrough
- Veterans Affairs San Diego Healthcare System, VA Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, United States
- Barbara O. Rothbaum
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Peter Roy-Byrne
- 5Department of Psychology, University of Washington, Seattle, WA, United States
- Soraya Seedat
- 1Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Soraya Seedat
- 2South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa
- Alicia K. Smith
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Alicia K. Smith
- 9Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, United States
- Jennifer S. Stevens
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States
- Leigh Luella van den Heuvel
- 1Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Leigh Luella van den Heuvel
- 2South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa
- Joanne Voisey
- 4School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia
- Joanne Voisey
- 3Center for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD, Australia
- Ross McD Young
- 6School of Psychology and Counseling, Queensland University of Technology, Kelvin Grove, QLD, Australia
- Lori A. Zoellner
- 7Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States
- Caroline M. Nievergelt
- Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
- Caroline M. Nievergelt
- Veterans Affairs San Diego Healthcare System, VA Center of Excellence for Stress and Mental Health (CESAMH), San Diego, CA, United States
- Erika J. Wolf
- 5National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, United States
- Erika J. Wolf
- 6Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fnins.2021.678503
- Journal volume & issue
-
Vol. 15
Abstract
Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study – United Kingdom Biobank – PTSD symptoms were negatively associated with SBP levels (β = −1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.
Keywords