Polygenic risk scoring to assess genetic overlap and protective factors influencing posttraumatic stress, depression, and chronic pain after motor vehicle collision trauma

Abstract

Posttraumatic stress (PTS), depressive symptoms (DS), and musculoskeletal pain (MSP) are common sequelae of trauma exposure. Although these adverse posttraumatic neuropsychiatric sequelae (APNS) are often studied separately, clinical comorbidity is high. In a cohort of European American motor vehicle collision (MVC) trauma survivors (n = 781), substantial PTS (≥33, IES-R), DS (≥26, CES-D), and MSP (≥4, 0–10 NRS) were identified via a 6-month survey. Genetic risk was estimated using polygenic risk scores (PRSs) calculated from the largest available GWAS datasets of PTSD, MDD, and back pain. We then assessed comorbidity and genetic risk influence for developing chronic PTS, DS, and MSP after MVC. Secondary analyses explored whether common social determinants of health ameliorate genetic vulnerability. We found that 6 months after MVC, nearly half 357/781 (46%) of the participants had substantial PTS, DS, and/or MSP, and overlap was common (PTS + MSP (23%), DS + MSP (18%), PTS + DS (12%)). Genetic risk predicted post-MVC outcomes. PTSD-PRSs predicted PTS and DS (R2 = 2.21% and 2.77%, padj < 0.01), MDD-PRSs predicted DS and MSP (R2 = 1.89%, padj < 0.01) and 0.79%, padj < 0.05), and back pain-PRS predicted MSP (R2 = 1.49%, padj < 0.01). Individuals in the highest quintile of PTSD-PRSs had 2.8 and 3.5 times the odds of developing PTS and DS vs. the lowest quintile (95% CI = 1.39–5.75 and 1.58–7.76). Among these high-risk individuals, those living in non-disadvantaged neighborhoods and with college education had 47% (p = 0.048) and 52% (p = 0.04) less risk of developing PTS, and those with high social support had 60% (p = 0.008) less risk of developing DS. Overall, genetic factors influence the risk of APNS after MVC, genetic risk of distinct APNS are overlapping, and specific social determinants greatly augment genetic risk of APNS development after MVC.

Risk Factors for Developing Concurrent Posttraumatic Stress Injury After Work-Related Musculoskeletal Injury

“…Our findings are consistent with suggestions that early clinical ratings of pain and disability or other patient-reported psychological or stress-related screening tools could help identify those most at risk of PTSI after MSI. 4 , 9 , 11 Further research is needed on preexisting mental health conditions or exposures to psychological trauma and risk of developing PTSI. Previous mental health problems may lower resilience in the face of MSI or other trauma as well as increase the risk of poor PTSI outcomes.…”

“…Other studies have identified that acute pain severity and associated psychological symptoms, such as catastrophizing, fear avoidance, low self-efficacy, and emotional problems, are also associated with development of PTSI symptoms 6–10 . These clinical characteristics are known to be influenced by physiological, social, and cultural factors 11 …”

“… 6 – 10 These clinical characteristics are known to be influenced by physiological, social, and cultural factors. 11 …”

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

“…1 Over the past decade however, large-scale genomewide association studies (GWAS) have made inroads towards elucidating the biological pathways and complex traits contributing to a wide range of conditions such as neurological, psychiatric & cardiometabolic disorders. 2 While such studies have provided evidence for genetically supported therapeutic targets & mechanisms, 3,4 the application of statistical genetics methods to musculoskeletal [5][6][7][8][9][10][11][12][13][14][15][16][17] and chronic pain conditions [18][19][20][21][22][23][24][25] as a strategy towards disentangling their causal mechanisms requires further comprehensive & concerted effort.…”

Snoring-related polygenic risk and its relationship with lifestyle factors in a Korean population: KoGES study

“…Polygenic scores predicted recent snoring and probable obstructive sleep apnea in an independent Australian sample (n = 8000). A potential causal relationship between high BMI and snoring was suggested based on Mendelian randomization analysis results.Several studies have compared PRSs by applying genetic analysis of speci c phenotypes to other independent group data[19][20][21][22][23][24]. According to a previous study that assessed PRSs for coronary artery disease and type 2 diabetes as predictive factors for cardiovascular (CV) mortality[21], both CAD PRS (low vs. very high genetic risk groups, CAD PRS hazard ratio [HR] 2.61 [2.02-3.36]) and T2DM PRS (HR 2.08 [1.58-2.73]) were signi cantly correlated with CV mortality risk.…”