Polygenic scores for empathy associate with posttraumatic stress severity in response to certain traumatic events

Frank R Wendt; Varun Warrier; Gita A Pathak; Karestan C Koenen; Murray B Stein; John H Krystal; Robert H Pietrzak; Joel Gelernter; Elizabeth V Goldfarb; Simon Baron-Cohen; Renato Polimanti

doi:10.1016/j.ynstr.2022.100439

Polygenic scores for empathy associate with posttraumatic stress severity in response to certain traumatic events

Neurobiol Stress. 2022 Feb 21:17:100439. doi: 10.1016/j.ynstr.2022.100439. eCollection 2022 Mar.

Authors

Frank R Wendt^{1

2}, Varun Warrier³, Gita A Pathak^{1

2}, Karestan C Koenen^{4

5

6}, Murray B Stein^{7

8

9}, John H Krystal^{1

10}, Robert H Pietrzak^{1

10

11}, Joel Gelernter^{1

2

12

13}, Elizabeth V Goldfarb^{1

14

15}, Simon Baron-Cohen³, Renato Polimanti^{1

2}

Affiliations

¹ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
² VA CT Healthcare System, West Haven, CT, USA.
³ Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
⁴ Broad Institute of MIT and Harvard, Stanley Center for Psychiatry Research, Cambridge, MA, USA.
⁵ Massachusetts General Hospital, Psychiatry and Neurodevelopmental Genetics Unit (PNGU), Boston, MA, USA.
⁶ Harvard School of Public Health, Department of Epidemiology, Boston, MA, USA.
⁷ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
⁸ Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
⁹ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
¹⁰ National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA.
¹¹ Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, USA.
¹² Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
¹³ Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
¹⁴ Yale Stress Center, Yale University School of Medicine, New Haven, CT, USA.
¹⁵ Department of Psychology, Yale School of Medicine, New Haven, CT, USA.

Abstract

Background: Posttraumatic stress disorder (PTSD) is triggered by environmental stressors. Empathy may predispose an individual to respond to life events differently if high empathizers are emotionally more sensitive to trauma. For the first time, we test this hypothesis using genetic information.

Methods: We applied polygenic scoring (PGS) to investigate the shared genetics linking empathy (measured using the Empathy Quotient (EQ), a self-report measure of empathy; N = 46,861) and PTSD symptom severity (measured using the 6-item PTSD Checklist 6-item (PCL-6)) in the UK Biobank (N = 126,219). Follow-up analyses were performed in the context of (1) experiencing any of 16 potential traumas, (2) the total number of traumas endorsed, and (3) the context of trauma. Autism, depression, generalized anxiety, and PCL-17 PGS were included as covariates to verify the specificity of the effect.

Results: EQ_PGS associated with PCL-6 (R ² = 0.012%, P = 9.35 × 10^-5). This effect remained significant after accounting for autism, depression, PTSD, and anxiety PGS but was observed only in those who endorsed experiencing at least one traumatic event. EQ_PGS showed the strongest effect on PCL-6 (β = 2.32, s.e. = 0.762, P = 0.002) among those who endorsed childhood neglect/abuse (felt hated as a child). With respect to case status, the highest probability of PTSD was 17.93% and 10.04% for those who endorsed "feeling hated as a child" and those who did not, respectively (P _diff = 0.011; Cohen's d = 1.951, 95%CI 1.70-2.20).

Conclusions: A genetic predisposition to higher empathy, which may index greater emotional sensitivity, predisposes an individual to more severe PTSD symptoms, especially after early-life adversity.

Keywords: Autism spectrum disorder; Empathizing; Pleiotropy; Polygenic score; Posttraumatic stress disorder; Trauma.

Abstract

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