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

Jarred J Lobo,Robert A Swor,Andrew S Tungate,Sarah D Linnstaedt,Niels K Rathlev,David A Peak,Samuel A Mclean,Phyllis L Hendry

doi:10.1038/s41398-021-01486-5

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.

Highlights

Adverse posttraumatic neuropsychiatric sequelae (APNS), such as posttraumatic stress (PTS), depressive symptoms (DS), and musculoskeletal pain (MSP), are common and morbid following traumatic experiences [1, 2]
We showed that genetic risk of developing APNS after motor vehicle collisions (MVCs) is overlapping, demonstrating that vulnerability to comorbid APNS outcomes after MVC is partly genetic in origin
We found that specific modifiable environmental risk factors interact with genetic vulnerability, possibly decreasing the likelihood of an individual with genetic vulnerability, who is involved in an MVC developing one or more APNS

Summary

Introduction

Adverse posttraumatic neuropsychiatric sequelae (APNS), such as posttraumatic stress (PTS), depressive symptoms (DS), and musculoskeletal pain (MSP), are common and morbid following traumatic experiences [1, 2]. One of the most common traumatic events in industrialized nations, motor vehicle collisions (MVCs), result in 50 million injuries worldwide and almost 4 million US emergency department (ED) visits each year [3, 4]. In the United States, ~90% of individuals presenting to the ED after MVC are discharged to home after evaluation and many subsequently develop APNS [5,6,7]. Most studies of MVC trauma survivors have focused on the study of individual APNS, available literature indicates that clinical comorbidity between them is high [8,9,10,11,12,13]. Factors contributing to APNS comorbidity after MVC remain poorly understood. Evidence from other settings suggests that shared genetic vulnerability factors may contribute to APNS comorbidity after MVC. Results from large genome-wide association studies (GWASs) estimate heritability for these outcomes to be

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Conclusion