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2. (Complex) PTSD in Ukrainian refugees:Prevalence and association with acts of war in the Danish refugee cohort (DARECO)

Author

Karstoft, K. I., Korchakova, N., Koushede, V. J., Morton, T. A., Pedersen, A. A., Power, S. A., Thøgersen, M. H., Karstoft, K. I., Korchakova, N., Koushede, V. J., Morton, T. A., Pedersen, A. A., Power, S. A., and Thøgersen, M. H.

Abstract

Background: The Russian invasion of Ukraine has driven millions of Ukrainians away from their homes. Among these, the majority have likely experienced war-related potentially traumatic events, and some will experience symptoms of posttraumatic stress disorder (PTSD). The aims of the study are to estimate the prevalence of PTSD and Complex PTSD (CPTSD) in displaced Ukrainians and examine associations between war- and other potentially traumatic exposures and (C)PTSD. Methods: Questionnaires were distributed to all registered adult Ukrainians (18+) who arrived in Denmark between February 24th 2022 and February 15th 2023 (N = 18,389). We estimate the prevalence of war exposures, other potentially traumatic exposures, and (C)PTSD. In logistic regression analyses, we test if exposure to war and other potentially traumatic events are associated with PTSD and CPTSD. Results: The final sample size was 6993 (38.0 %). Responders were more likely to be female and younger than non-responders. Prevalence of PTSD and CPTSD was 15.9 % and 13.5 %, respectively. Female gender, high education, and loss of a relative due to the war were associated with (C)PTSD. Direct and indirect exposure to war and combat was related to PTSD but not CPTSD, while exposure to war prior to the 2022 invasion was related to CPTSD but not PTSD. Limitations: The study is cross-sectional and based on self-report. Conclusion: Close to one third of the sample fulfill the criteria of PTSD or CPTSD. War exposures are differentially related to PTSD and CPTSD. The findings illustrate that trauma-related psychopathology is a pertinent problem in displaced Ukrainians.

Published
2024

3. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, AX, Choi, KW, Coleman, JR, Daskalakis, NP, Denckla, CA, Ketema, E, Morey, RA, Polimanti, R, Ratanatharathorn, A, Torres, K, Wingo, AP, Zai, CC, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Borglum, AD, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Chen, C-Y, Dale, AM, Dalvie, S, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Duncan, LE, Kulenovic, AD, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gautam, A, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goci, A, Gordon, SD, Guffanti, G, Hammamieh, R, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, JL, Marmar, C, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Michopoulos, V, Milberg, W, Miller, MW, Morris, CP, Mors, O, Mortensen, PB, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Haas, M, Lasseter, H, Provost, AC, Salem, RM, Sebat, J, Shaffer, RA, Wu, T, Ripke, S, Daly, MJ, Ressler, KJ, Koenen, KC, Stein, MB, Nievergelt, CM, Maihofer, AX, Choi, KW, Coleman, JR, Daskalakis, NP, Denckla, CA, Ketema, E, Morey, RA, Polimanti, R, Ratanatharathorn, A, Torres, K, Wingo, AP, Zai, CC, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Borglum, AD, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Chen, C-Y, Dale, AM, Dalvie, S, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Duncan, LE, Kulenovic, AD, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gautam, A, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goci, A, Gordon, SD, Guffanti, G, Hammamieh, R, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, JL, Marmar, C, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Michopoulos, V, Milberg, W, Miller, MW, Morris, CP, Mors, O, Mortensen, PB, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Haas, M, Lasseter, H, Provost, AC, Salem, RM, Sebat, J, Shaffer, RA, Wu, T, Ripke, S, Daly, MJ, Ressler, KJ, Koenen, KC, Stein, MB, and Nievergelt, CM

Abstract

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

4. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

Schijven, D., Chen, C.-Y., Morey, R.A., Vermetten, E., Sanchez, S.E., Maihofer, A.X., Jett, M., Dale, A.M., Ratanatharathorn, A., McGlinchey, R.E., McLaughlin, K.A., Polimanti, R., Roberts, A.L., Williams, M.A., Nievergelt, C.M., Atkinson, E.G., Mors, O., Brashear, M., Gordon, S.D., Trapido, E., Haas, M., Lawford, B.R., Kimbrel, N.A., Sponheim, S.R., Daskalakis, N.P., Duncan, L.E., Rung, A., Orcutt, H.K., Pietrzak, R.H., Bustamante, A.C., Bisson, J.I., Koenen, K.C., McLean, S.A., Ripke, S., Kremen, W.S., Maples-Keller, J., Marmar, C., Sheerin, C.M., Calabrese, J.R., Andersen, S.B., Seligowski, A.V., Feeny, N.C., Polusny, M.A., Qin, X.-J., Daly, M.J., Ashley-Koch, A.E., Morris, C.P., Liberzon, I., Erbes, C.R., King, A.P., Zhao, H., Forbes, D., Jakovljevic, M., van den Heuvel, L.L., Peters, E.S., Evans, A., Boks, M.P., Aiello, A.E., Hougaard, D.M., Roy-Byrne, P., Bierut, L.J., Kranzler, H.R., Vinkers, C.H., Peterson, A.L., Wolf, C., Deckert, J., Linnstaedt, S.D., Stein, D.J., Levey, D.F., Almli, L.M., Martin, N.G., Williamson, D.E., Flory, J.D., Børglum, A.D., Guffanti, G., Stein, M.B., Lori, A., Khan, A., Baker, D.G., Ressler, K.J., Torres, K., Seedat, S., Andreassen, O.A., Neale, B.M., Werge, T., Mehta, D., Austin, S.B., Breen, G., Beckham, J.C., Geuze, E., Miller, M.W., Mortensen, P.B., Coleman, J.R.I., Provost, A.C., Norman, S.B., Garrett, M.E., McLeay, S., Van Hooff, M., Bolger, E.A., Franz, C.E., Luykx, J.J., Maurer, D., Wolff, J.D., Martin, A.R., Young, K.A., Lewis, C.E., Zoellner, L.A., Dennis, M.F., Delahanty, D.L., O’Donnell, M., Heath, A.C., Saccone, N.L., Domschke, K., Logue, M.W., Ursano, R.J., Smith, A.K., Rothbaum, A.O., Rutten, B.P.F., Harnal, S., Panizzon, M.S., Uddin, M., Babiat, D., Bryant, R.A., Gelernter, J., Smoller, J.W., Klengel, T., Bybjerg-Grauholm, J., Choi, K.W., Jovanovic, T., Caldas-de-Almeida, J.M., Nelson, E.C., Mavissakalian, M.R., Johnson, E.O., Hammamieh, R, Milberg, W.P., Nordentoft, M., Gillespie, C., Amstadter, A.B., Bradley, B., Teicher, M.H., Arbisi, P.A., Lebois, L.A.M., Hauser, M.A., Dzubur-Kulenovic, A., Hemmings, S.M.J., Gelaye, B., Sumner, J.A., Uka, A.G., Young, R.M.D., Voisey, J., Wang, Y., Galea, S., Wang, Z., Jones, I., Peverill, M., Disner, S.G., Seng, J.S., Kessler, R.C., Junglen, A.G., Wolf, E.J., Lugonja, B., Dalvie, S., Koen, N., Rice, J.P., Rothbaum, B.O., Thompson, W.K., Ruggiero, K., Karstoft, K.-I., Farrer, L.A., Stevens, J.S., Silove, D., Avdibegovic, E., Risbrough, V.B., Lyons, M.J., Bækvad-Hansen, M., and McFarlane, A.

Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2019
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5. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

Nievergelt, CM, Maihofer, AX, Klengel, T, Atkinson, EG, Chen, C-Y, Choi, KW, Coleman, JR, Dalvie, S, Duncan, LE, Gelernter, J, Levey, DF, Logue, MW, Polimanti, R, Provost, AC, Ratanatharathorn, A, Stein, MB, Torres, K, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Brglum, AD, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Dale, AM, Daly, MJ, Daskalakis, NP, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Dzubur-Kulenovic, A, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gelaye, B, Geuze, E, Gillespie, C, Uka, AG, Gordon, SD, Guffanti, G, Hammamieh, R, Harnal, S, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Junglen, AG, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, CE, Linnstaedt, SD, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, J, Marmar, C, Martin, AR, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, McLeay, S, Mehta, D, Milberg, WP, Miller, MW, Morey, RA, Morris, CP, Mors, O, Mortensen, PB, Neale, BM, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Ripke, S, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, K, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Sumner, JA, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Wolff, JD, Yehuda, R, Young, RM, Young, KA, Zhao, H, Zoellner, LA, Liberzon, I, Ressler, KJ, Haas, M, Koenen, KC, Nievergelt, CM, Maihofer, AX, Klengel, T, Atkinson, EG, Chen, C-Y, Choi, KW, Coleman, JR, Dalvie, S, Duncan, LE, Gelernter, J, Levey, DF, Logue, MW, Polimanti, R, Provost, AC, Ratanatharathorn, A, Stein, MB, Torres, K, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Brglum, AD, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Dale, AM, Daly, MJ, Daskalakis, NP, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Dzubur-Kulenovic, A, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gelaye, B, Geuze, E, Gillespie, C, Uka, AG, Gordon, SD, Guffanti, G, Hammamieh, R, Harnal, S, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Junglen, AG, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, CE, Linnstaedt, SD, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, J, Marmar, C, Martin, AR, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, McLeay, S, Mehta, D, Milberg, WP, Miller, MW, Morey, RA, Morris, CP, Mors, O, Mortensen, PB, Neale, BM, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Ripke, S, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, K, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Sumner, JA, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Wolff, JD, Yehuda, R, Young, RM, Young, KA, Zhao, H, Zoellner, LA, Liberzon, I, Ressler, KJ, Haas, M, and Koenen, KC

Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Published
2019

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