Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Jessica Mundy; Christopher Hübel; Joel Gelernter; Daniel Levey; Robin M Murray; Megan Skelton; Murray B Stein; Evangelos Vassos; Gerome Breen; Jonathan R I Coleman; Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1017/S0033291721000830

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Jessica Mundy, Christopher Hübel, Joel Gelernter, Daniel Levey, Robin M Murray, Megan Skelton, Murray B Stein, Evangelos Vassos, Gerome Breen, Jonathan R I Coleman, Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium

PoNE - Attitudes - social welfare - cheaters

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

11 Citationer (Scopus)

Abstract

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 (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced singleepisode MDD (X2 > 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.

Originalsprog	Engelsk
Tidsskrift	Psychological Medicine
Vol/bind	52
Nummer	16
Sider (fra-til)	1-10
Antal sider	10
ISSN	0033-2917
DOI	https://doi.org/10.1017/S0033291721000830
Status	Udgivet - jun. 2021

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10.1017/S0033291721000830

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Mundy, J., Hübel, C., Gelernter, J., Levey, D., Murray, R. M., Skelton, M., Stein, M. B., Vassos, E., Breen, G., Coleman, J. R. I., & Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium (2021). Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. Psychological Medicine, 52(16), 1-10. https://doi.org/10.1017/S0033291721000830

@article{42ee2a80a73e41158b0e4e4bcd77ce95,

title = "Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder",

abstract = "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 (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced singleepisode MDD (X2 > 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.",

keywords = "Genetic correlations, Genetics, Major depressive disorder, Polygenic risk scores, Posttraumatic stress disorder, Psychological trauma",

author = "Jessica Mundy and Christopher H{\"u}bel and Joel Gelernter and Daniel Levey and Murray, {Robin M} and Megan Skelton and Stein, {Murray B} and Evangelos Vassos and Gerome Breen and Coleman, {Jonathan R I} and {Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium}",

year = "2021",

month = jun,

doi = "10.1017/S0033291721000830",

language = "English",

volume = "52",

pages = "1--10",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "16",

}

Mundy, J, Hübel, C, Gelernter, J, Levey, D, Murray, RM, Skelton, M, Stein, MB, Vassos, E, Breen, G, Coleman, JRI & Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium 2021, 'Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder', Psychological Medicine, bind 52, nr. 16, s. 1-10. https://doi.org/10.1017/S0033291721000830

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder. / Mundy, Jessica; Hübel, Christopher; Gelernter, Joel et al.
I: Psychological Medicine, Bind 52, Nr. 16, 06.2021, s. 1-10.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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 - 2021/6

Y1 - 2021/6

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 (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced singleepisode MDD (X2 > 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 (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced singleepisode MDD (X2 > 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 - Genetic correlations

KW - Genetics

KW - Major depressive disorder

KW - Polygenic risk scores

KW - Posttraumatic stress disorder

KW - Psychological trauma

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U2 - 10.1017/S0033291721000830

DO - 10.1017/S0033291721000830

M3 - Journal article

C2 - 34085609

SN - 0033-2917

VL - 52

SP - 1

EP - 10

JO - Psychological Medicine

JF - Psychological Medicine

IS - 16

ER -

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

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