New research reveals how a person’s genetics and trauma symptoms combine to affect their tobacco use after a distressing event. The findings suggest that people with a lower genetic predisposition for tobacco use might actually be more vulnerable to smoking when experiencing specific trauma symptoms. The large study was published in Translational Psychiatry.
About 70 percent of people experience a traumatic event during their lifetime. Roughly 10 percent of those individuals go on to develop post-traumatic stress disorder, or PTSD. People with PTSD frequently struggle with substance use, including tobacco and alcohol consumption. Both PTSD and substance use behaviors are influenced by a mix of life experiences and biological factors.
Past research has linked PTSD to higher rates of smoking and drinking. What is less understood is how trauma symptoms interact with a person’s underlying genetic risk for substance use. Substance use behavior is heavily influenced by genetics, with many small variations in a person’s DNA contributing to their overall risk.
Researchers calculate this cumulative biological vulnerability using a mathematical tool called a polygenic risk score. A polygenic risk score works by scanning thousands of genetic variations across a person’s genome. Researchers assign a weight to each variation based on how strongly it links to a trait, and then they add those weights together to create a single score.
Most previous studies looking at how genes and the environment interact have focused on isolated genetic markers or populations of entirely European descent. Henri M. Garrison-Desany, a researcher at the Harvard T.H. Chan School of Public Health, led a team to investigate how overall genetic risk and trauma interact in a diverse group of people. The researchers wanted to see if specific elements of PTSD had distinct relationships with substance use when factoring in genetic risk.
The team analyzed data from 2,973 adults who had recently experienced a traumatic event. The participants were recruited within 72 hours of visiting an emergency department. The most common traumatic event reported was a motor vehicle collision, followed by physical or sexual assaults. The participants provided blood samples, which the team used to extract DNA and calculate polygenic risk scores for tobacco and alcohol use.
Because genetic research has historically overrepresented people of European descent, standard genetic risk scores often perform poorly in diverse populations. To address this bias, the researchers used a specialized statistical method designed to estimate genetic risk across multiple ancestries. The study group included individuals of predominantly African, European, and admixed American ancestries.
The participants completed surveys to track their mental health and behavior over the following months. The researchers measured PTSD symptoms at eight weeks after the initial trauma. They then looked at how often and how much the participants smoked or drank alcohol at six months after the event. The team divided PTSD symptoms into four categories: avoidance, hyperarousal, negative cognition and mood, and re-experiencing the trauma.
When looking at the genetic scores alone, the researchers found that higher polygenic risk scores for tobacco were associated with an increase in the risk of using tobacco at the six-month mark. The genetic scores for alcohol use did not show consistent associations with drinking behavior across the entire diverse cohort. The alcohol genetic score only reliably predicted drinking behavior in the subgroup of participants with European ancestry.
Next, the researchers examined how PTSD symptoms and genetic risk interacted. They found that trauma symptoms and genetic predisposition did not simply add together to create a massive risk for tobacco use. Instead, they observed an antagonistic effect. The association between trauma symptoms and subsequent tobacco use was weaker for individuals who already had a high genetic risk for tobacco use.
Conversely, people with a lower genetic risk for tobacco use showed a stronger association between their trauma symptoms and their smoking habits. If a person was not biologically predisposed to use tobacco, experiencing high levels of post-traumatic stress was linked to a noticeable increase in smoking. This suggests that people with a lower baseline risk might be highly sensitive to the environmental stress of a trauma.
This pattern was particularly apparent for two specific types of PTSD symptoms. Re-experiencing symptoms, such as flashbacks or nightmares, interacted strongly with the genetic scores. A similar interaction appeared for negative alterations in cognition and mood, which involves persistent negative emotions or distorted beliefs about oneself. For both of these symptom categories, the participants with the lowest genetic risk showed the sharpest increase in tobacco use in response to the symptoms.
The researchers did not find this type of interaction between PTSD symptoms and the genetic risk for alcohol consumption. Alcohol use was highly prevalent among the participants before the trauma occurred, which might have masked any changes related to the traumatic event itself. In addition, the genetic scores for alcohol were not consistently associated with drinking when adjusting for prior mental health conditions.
The study relies on self-reported survey data to measure substance use, which can introduce errors if participants underreport their habits. The types of trauma experienced by the participants were also heavily skewed toward car accidents. Other types of trauma, such as combat exposure or chronic abuse, often result in different symptom profiles that might interact differently with genetic risk.
While the researchers used advanced methods to account for diverse ancestries, the underlying genetic reference data still largely stems from European populations. As a result, the genetic risk scores remained most accurate for participants of European descent and underperformed in individuals of African and Indigenous American ancestries. Building more diverse genetic databases is a necessary step for making polygenic risk scores accurate for the general public.
These results point toward a threshold effect for substance use risk among trauma survivors. If a person already possesses a high biological risk for smoking, the added stress of a trauma might not elevate their risk much further. In contrast, those without a high genetic risk are more visibly affected by the onset of trauma symptoms. Identifying the specific symptoms that drive people to use substances could eventually help clinicians tailor treatments for trauma survivors based on their unique symptom profiles.
The study, “Post-traumatic stress and genetic interactions affect tobacco and alcohol use after trauma: findings from a multi-ancestry cohort,” was authored by Henri M. Garrison-Desany, Cecilia A. Hinojosa, Justin D. Tubbs, Jacquelyn L. Meyers, Sarah D. Linnstaedt, Stacey L. House, Francesca L. Beaudoin, Xinming An, Jennifer S. Stevens, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Paul I. Musey Jr, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Jose L. Pascual, Mark J. Seamon, Erica Harris, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Brian J. O’Neil, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Kerry J. Ressler, Karestan C. Koenen, and Christy A. Denckla.
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