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Higher polygenic scores for empathy increase posttraumatic stress severity in response to certain traumatic events

By 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

Posted 30 Jul 2021
medRxiv DOI: 10.1101/2021.07.26.21261139

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 at the genetic level. 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 EQPGS associated with PCL-6 (R2=0.012%, P=9.35x10-5). 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. EQPGS showed the strongest effect on PCL-6 (beta=2.32, s.e.=0.762, P=0.002) among those who endorsed childhood neglect/abuse (felt hated as a child). In the highest EQPGS decile, feeling hated as a child was associated with lower odds of healthy adulthood interpersonal relationships (OR=0.623, 95%CI 0.443-0.885) but this association was not seen in the lowest EQPGS decile. Conclusions A genetic predisposition to higher empathy, which may index greater emotional sensitivity, predisposes an individual to more severe PTSD symptoms, specifically in the presence of early negative life events.

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