Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

Autor: Wani AH; Genomics Program, College of Public Health, University of South Florida, Tampa, FL, USA., Katrinli S; Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA., Zhao X; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Daskalakis NP; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA.; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; Center of Excellence in Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA., Zannas AS; University of North Carolina at Chapel Hill, Carolina Stress Initiative, Chapel Hill, NC, USA.; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Aiello AE; Robert N Butler Columbia Aging Center, Department of Epidemiology, Columbia University, New York, NY, USA., Baker DG; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Psychiatry Service, San Diego, CA, USA., Boks MP; Department of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht, UT, Netherlands., Brick LA; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA., Chen CY; Biogen Inc., Translational Sciences, Cambridge, MA, USA., Dalvie S; Department of Pathology, University of Cape Town, Cape Town, Western Province, South Africa.; Division of Human Genetics, University of Cape Town, Cape Town, Western Province, South Africa., Fortier C; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; VA Boston Healthcare System, TRACTS/GRECC, Boston, MA, USA., Geuze E; Brain Research and Innovation Centre, Netherlands Ministry of Defence, Utrecht, UT, Netherlands.; Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, UT, Netherlands., Hayes JP; Department of Psychology, The Ohio State University, Columbus, OH, USA., Kessler RC; Department of Health Care Policy, Harvard Medical School, Boston, MA, USA., King AP; The Ohio State University, College of Medicine, Institute for Behavioral Medicine Research, Columbus, OH, USA., Koen N; Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, Western Province, South Africa.; University of Cape Town, Neuroscience Institute, Cape Town, Western Province, South Africa.; SA MRC Unit On Risk & Resilience in Mental Disorders, University of Cape Town, Cape Town, Western Province, South Africa., Liberzon I; Department of Psychiatry and Behavioral Sciences, Texas A&M University College of Medicine, Bryan, TX, USA., Lori A; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Luykx JJ; Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, UT, Netherlands.; Department of Translational Neuroscience, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, UT, Netherlands., Maihofer AX; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA., Milberg W; VA Boston Healthcare System, GRECC/TRACTS, Boston, MA, USA., Miller MW; Boston University School of Medicine, Psychiatry, Boston, MA, USA.; VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA., Mufford MS; University of Cape Town, Neuroscience Institute, Cape Town, Western Province, South Africa.; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Province, South Africa., Nugent NR; Department of Emergency Medicine, Warren Alpert Brown Medical School, Providence, RI, USA.; Department of Pediatrics, Warren Alpert Brown Medical School, Providence, RI, USA.; Department of Psychiatry and Human Behavior, Warren Alpert Brown Medical School, Providence, RI, USA., Rauch S; Department of Psychiatry & Behavioral Sciences, Emory University, Atlanta, GA, USA.; Joseph Maxwell Cleland Atlanta Veterans Affairs Medical Center, Mental Health Service Line, Atlanta, USA., Ressler KJ; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.; McLean Hospital, Belmont, MA, USA., Risbrough VB; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA., Rutten BPF; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht Universitair Medisch Centrum, Maastricht, Limburg, Netherlands., Stein DJ; Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, Western Province, South Africa.; University of Cape Town, Neuroscience Institute, Cape Town, Western Province, South Africa.; SA MRC Unit On Risk & Resilience in Mental Disorders, University of Cape Town, Cape Town, Western Province, South Africa., Stein MB; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Psychiatry Service, San Diego, CA, USA.; School of Public Health, University of California San Diego, La Jolla, CA, USA., Ursano RJ; Department of Psychiatry, Uniformed Services University, Bethesda, MD, USA., Verfaellie MH; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.; VA Boston Healthcare System, Memory Disorders Research Center, Boston, MA, USA., Vermetten E; Department of Psychiatry, Leiden University Medical Center, Leiden, ZH, Netherlands.; Department of Psychiatry, New York University School of Medicine, New York, NY, USA., Vinkers CH; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Holland, Netherlands.; Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Holland, Netherlands.; Department of Psychiatry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Holland, Netherlands., Ware EB; Survey Research Center, University of Michigan, Institute for Social Research, Ann Arbor, MI, USA., Wildman DE; Genomics Program, College of Public Health, University of South Florida, Tampa, FL, USA., Wolf EJ; VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA.; Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Nievergelt CM; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Veterans Affairs San Diego Healthcare System, Research Service, San Diego, CA, USA., Logue MW; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; VA Boston Healthcare System, National Center for PTSD, Boston, MA, USA.; Boston University School of Medicine, Psychiatry, Biomedical Genetics, Boston, MA, USA., Smith AK; Department of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.; Department of Human Genetics, Emory University, Atlanta, GA, USA., Uddin M; Genomics Program, College of Public Health, University of South Florida, Tampa, FL, USA. monica43@usf.edu.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2024 Sep 27; Vol. 17 (1), pp. 235. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1186/s12920-024-02002-6
Abstrakt: Background: Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not.
Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts.
Results: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD.
Conclusion: The inclusion of exposure variables adds to the predictive power of MRS. Classification-based MRS may be useful in predicting risk of future PTSD in populations with anticipated trauma exposure. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting PTSD and, relatedly, improve their performance in independent cohorts.
(© 2024. The Author(s).)
Databáze: MEDLINE
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