TY - JOUR
T1 - Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
AU - Mundy, Jessica
AU - Hübel, Christopher
AU - Gelernter, Joel
AU - Levey, Daniel
AU - Murray, Robin M
AU - Skelton, Megan
AU - Stein, Murray B
AU - Vassos, Evangelos
AU - Breen, Gerome
AU - Coleman, Jonathan R I
AU - Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium
PY - 2022/12/4
Y1 - 2022/12/4
N2 - Background. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Methods. Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Results. Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (r
g differences = ∼0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ
2 > 166, p < 0.001) Conclusions. Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.
AB - Background. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Methods. Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Results. Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (r
g differences = ∼0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ
2 > 166, p < 0.001) Conclusions. Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.
KW - Posttraumatic stress disorder
KW - genetic correlations
KW - genetics
KW - major depressive disorder
KW - polygenic risk scores
KW - psychological trauma
UR - http://www.scopus.com/inward/record.url?scp=85108071940&partnerID=8YFLogxK
U2 - 10.1017/S0033291721000830
DO - 10.1017/S0033291721000830
M3 - Journal article
C2 - 34085609
SN - 0033-2917
VL - 52
SP - 3975
EP - 3984
JO - Psychological Medicine
JF - Psychological Medicine
IS - 16
ER -