Post-traumatic stress and genetic interactions affect tobacco and alcohol use after trauma: findings from a multi-ancestry cohort

Henri M Garrison-Desany¹, Cecilia A Hinojosa², Justin D Tubbs^{3

4

5}, Jacquelyn L Meyers⁶, Sarah D Linnstaedt⁷, Stacey L House⁸, Francesca L Beaudoin^{9

10}, Xinming An⁷, Jennifer S Stevens², Thomas C Neylan¹¹, Gari D Clifford^{12

13}, Laura T Germine^{14

15

16}, Scott L Rauch^{14

16

17}, John P Haran¹⁸, Alan B Storrow¹⁹, Paul I Musey Jr²⁰, Phyllis L Hendry²¹, Sophia Sheikh²¹, Christopher W Jones²², Brittany E Punches^{23

24}, Jose L Pascual^{25

26}, Mark J Seamon^{26

27}, Erica Harris²⁸, Claire Pearson²⁹, David A Peak^{30

31}, Roland C Merchant³², Robert M Domeier³³, Brian J O'Neil³⁴, Paulina Sergot³⁵, Leon D Sanchez^{31

32}, Steven E Bruce³⁶, Steven E Harte^{37

38}, Samuel A McLean^{39

40}, Kerry J Ressler^{16

41}, Karestan C Koenen⁴², Christy A Denckla⁴³

Affiliations

¹ Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA. mgarris7@jhu.edu.
² Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
³ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁵ Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA.
⁶ Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, New York, NY, USA.
⁷ Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁹ Department of Epidemiology, Brown University, Providence, RI, USA.
¹⁰ Department of Emergency Medicine, Brown University, Providence, RI, USA.
¹¹ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
¹² Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
¹³ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹⁴ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁵ The Many Brains Project, Belmont, MA, USA.
¹⁶ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹⁷ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁸ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁹ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁰ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
²¹ Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, USA.
²² Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
²³ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA.
²⁴ Ohio State University College of Nursing, Columbus, OH, USA.
²⁵ Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁶ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA, USA.
²⁹ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
³⁰ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
³¹ Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³² Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³³ Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
³⁴ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³⁵ Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, TX, USA.
³⁶ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁷ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁸ Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁹ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Institute for Trauma Recovery, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴¹ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
⁴² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁴³ Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

PMID: 41136357
PMCID: PMC12552440
DOI: 10.1038/s41398-025-03593-z

Post-traumatic stress and genetic interactions affect tobacco and alcohol use after trauma: findings from a multi-ancestry cohort

Henri M Garrison-Desany et al. Transl Psychiatry. 2025.

. 2025 Oct 24;15(1):434.

doi: 10.1038/s41398-025-03593-z.

Authors

Affiliations

¹ Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA. mgarris7@jhu.edu.
² Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
³ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁵ Stanley Center for Psychiatric Research, Broad Institute, Boston, MA, USA.
⁶ Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, New York, NY, USA.
⁷ Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁹ Department of Epidemiology, Brown University, Providence, RI, USA.
¹⁰ Department of Emergency Medicine, Brown University, Providence, RI, USA.
¹¹ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
¹² Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
¹³ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹⁴ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁵ The Many Brains Project, Belmont, MA, USA.
¹⁶ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹⁷ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁸ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁹ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁰ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
²¹ Department of Emergency Medicine, University of Florida College of Medicine -Jacksonville, Jacksonville, FL, USA.
²² Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
²³ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA.
²⁴ Ohio State University College of Nursing, Columbus, OH, USA.
²⁵ Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁶ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA, USA.
²⁹ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
³⁰ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
³¹ Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³² Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³³ Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
³⁴ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³⁵ Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, TX, USA.
³⁶ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁷ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁸ Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
³⁹ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Institute for Trauma Recovery, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴¹ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
⁴² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁴³ Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

PMID: 41136357
PMCID: PMC12552440
DOI: 10.1038/s41398-025-03593-z

Abstract

Tobacco smoking and drinking alcohol are common substance use behaviors influenced by both genetic risk and environmental exposures. Traumatic events are highly prevalent, affecting about 70% of people in their lifetime. After trauma, it is unclear what role post-traumatic stress disorder (PTSD) symptoms play in substance use behaviors when accounting for this genetic risk. We used data from the Advancing Understanding of RecOvery afteR traumA (AURORA), which included 2973 participants recruited at emergency departments (EDs) within 72 h of a traumatic event and followed over time. We measured PTSD symptoms via PTSD Checklist for the DSM-5. Tobacco and alcohol consumption as frequency, quantity, and quantity-frequency in the past 30 days. We generated polygenic risk scores with continuous shrinkage for cross-ancestry estimation (PRS-CSx). We tested for main effects between PRS-CSx scores and interactions with PTSD using quasipoisson regression, with week 8 PTSD symptoms and month 6 substance use behaviors after the traumatic event. Tobacco PRS-CSx score increased the risk of tobacco use by 14% (95% CI: 1.01, 1.29, p = 0.03), and alcohol PRS-CSx score did not demonstrate consistent associations in the whole cohort (IRR: 1.08, 95% CI: 0.97, 1.19, p = 0.16). When stratified by ancestry group, both tobacco (IRR: 1.36, 95% CI: 1.14, 1.61, p < 0.001) and alcohol (IRR: 1.24, 95% CI: 1.07, 1.44, p = 0.005) PRS-CSx scores were associated with their respective outcomes in the European ancestry subcohort. Participants with lower genetic risk had stronger associations between re-experiencing symptoms and tobacco use, while participants with higher genetic risk demonstrated weaker association between re-experiencing symptoms and tobacco use. A similar pattern was observed for negative alterations in cognition/mood (NACM) symptoms-participants with lower PRS-CSx scores had stronger associations between NACM symptoms with tobacco use, compared to participants with higher PRS-CSx scores. These interactions were both statistically significant, suggesting an antagonistic effect between PRS-CSx scores and PTSD symptoms on tobacco use.

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Conflict of interest statement

Competing interests: Dr. Garrison-Desany has no competing interests related to this work, though received a contract from Indivior PLC from February to May 2025 for research unrelated to this manuscript. Dr. Hinojosa receives support from the National Institute of Alcohol Abuse and Alcoholism, K99AA031333. Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years Dr Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, and the Rett Research Foundation. Dr Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical with significant stock. These relationships are unconnected to the current work. Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Her family also has equity in Intelerad Medical Systems, Inc. Dr. Rauch reported serving as secretary of the Society of Biological Psychiatry; serving as a board member of Community Psychiatry and Mindpath Health; serving as a board member of National Association of Behavioral Healthcare; serving as secretary and a board member for the Anxiety and Depression Association of America; serving as a board member of the National Network of Depression Centers; receiving royalties from Oxford University Press, American Psychiatric Publishing Inc, and Springer Publishing; and receiving personal fees from the Society of Biological Psychiatry, Community Psychiatry and Mindpath Health, and National Association of Behavioral Healthcare outside the submitted work. Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Memorial Sloan Kettering Cancer Center, Indiana University, The Ohio State University, and Dana Farber Cancer Institute. Dr. McLean has served as a consultant for Walter Reed Army Institute for Research, Arbor Medical Innovations, and BioXcel Therapeutics, Inc. Dr. Ressler has performed scientific consultation for Bioxcel, Bionomics, Acer, and Jazz Pharma; serves on Scientific Advisory Boards for Sage, Boehringer Ingelheim, Senseye, and the Brain Research Foundation, and he has received sponsored research support from Alto Neuroscience. Dr. Koenen’s has been a paid scientific consultant for the US Department of Justice and Covington Burling, LLP over the last three years. She receives royalties from Guilford Press and Oxford University Press.

Figures

**Fig. 1. Percentile of tobacco-based PRS-CSx score and average tobacco use frequency at baseline, for all ancestries and stratified by estimated ancestry group.**
PRS-CSx scores were first centered and standardized, then converted to deciles for plotting. Ancestry groups were determined using ADMIXTURE software, and thresholds for likely ancestry were set at >0.90 in the factor loadings. The frequency of tobacco use was ascertained in the past 30 days of the emergency department (ED) baseline.

**Fig. 2. Percentile of alcohol-based PRS-CSx score and average alcohol use frequency at baseline, for all ancestries and stratified by estimated ancestry group.**
PRS-CSx scores were first centered and standardized, then converted to deciles for plotting. Ancestry groups were determined using ADMIXTURE software, and thresholds for likely ancestry were set at >0.90 in the factor loadings. The frequency of alcohol use was ascertained in the past 30 days of the emergency department (ED) baseline.

Fig. 3. Associations of polygenic risk scores (PRS) with tobacco frequency and quantity, and alcohol frequency and quantity 6 months after a traumatic event, adjusting for post-traumatic stress and lifetime traumatic events for all ancestries.
IRR: Incidence rate ratio as estimated using the quasipoisson model to relax dispersion parameter assumptions, 95% CI: 95% confidence interval. The outcome definition was the number of times one consumed the substance in the past 30 days, multiplied by the quantity consumed on average when one did consume, in the past 30 days. PRS-CSx: Polygenic risk score using continuous shrinkage and cross-ancestry methods; generated with summary statistics from the GSCAN database for average cigarette per week and average alcoholic drinks per week. PTS symptoms: Post-traumatic stress (PTS) was ascertained with the PTSD Checklist for the DSM-5 (PCL-5). Anxiety was ascertained with the PROMIS Anxiety Bank of state and trait anxiety. Depression was ascertained with the PROMIS 8-item short form for Depression. Ancestry-specific principal components were controlled for in all models.

Fig. 4. Main and joint effects of polygenic risk score (PRS) and post-traumatic stress (PTS) symptoms and subscales at 8 weeks post-trauma on tobacco use in the past 30 days at 6 months post-trauma for all ancestries.
¹PRS-CSx: Polygenic risk score using continuous shrinkage and cross-ancestry methods; generated with summary statistics from the GSCAN database for average cigarette per week and average alcoholic drinks per week. ²IRR: Incidence rate ratio as estimated using the quasipoisson model to relax dispersion parameter assumptions, 95% CI: 95% confidence interval. ³ PTSD: Post-traumatic stress, symptoms were assessed using the post-traumatic stress disorder (PTSD) symptom checklist for the DMS-5 (PCL-5), with relevant subscales also reported (re-experiencing, negative cognition and mood, hyperarousal, and avoidance). Models were also adjusted with 5 principal components for global ancestry, and 5 principal components calculated within the top 3 ancestry groups, determined by >90% of the genetic variance related to ancestry being explained by that component.

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References

1. Benjet C, Bromet E, Karam EG, Kessler RC, McLaughlin KA, Ruscio AM, et al. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol Med. 2016;46:327–43. - PMC - PubMed
1. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017;47:2260–74. - PMC - PubMed
1. Garrison-Desany HM, Meyers JL, Linnstaedt SD, House SL, Beaudoin FL, An X, et al. Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk. Front Psychiatry 2024;15. 10.3389/fpsyt.2024.1249382. - PMC - PubMed
1. Hinojosa CA, Liew A, An X, Stevens JS, Basu A, van Rooij SJH, et al. Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals. Psychol Med. 2024;54:338–49. - PMC - PubMed
1. Brady KT, McCauley JL, Back SE The comorbidity of Post-traumatic Stress Disorder (PTSD) and substance use disorders. In: el-Guebaly N, Carrà G, Galanter M, Baldacchino AM (eds). Textbook of addiction treatment: international perspectives. Cham: Springer International Publishing; 2021, pp 1327-39.

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Post-traumatic stress and genetic interactions affect tobacco and alcohol use after trauma: findings from a multi-ancestry cohort

Affiliations

Post-traumatic stress and genetic interactions affect tobacco and alcohol use after trauma: findings from a multi-ancestry cohort

Authors

Affiliations

Abstract

Conflict of interest statement

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References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous