Sumner Jennifer A, Maihofer Adam X, Michopoulos Vasiliki, Rothbaum Alex O, Almli Lynn M, Andreassen Ole A, Ashley-Koch Allison E, Baker Dewleen G, Beckham Jean C, Bradley Bekh, Breen Gerome, Coleman Jonathan R I, Dale Anders M, Dennis Michelle F, Feeny Norah C, Franz Carol E, Garrett Melanie E, Gillespie Charles F, Guffanti Guia, Hauser Michael A, Hemmings Sian M J, Jovanovic Tanja, Kimbrel Nathan A, Kremen William S, Lawford Bruce R, Logue Mark W, Lori Adriana, Lyons Michael J, Maples-Keller Jessica, Mavissakalian Matig R, McGlinchey Regina E, Mehta Divya, Mellor Rebecca, Milberg William, Miller Mark W, Morris Charles Phillip, Panizzon Matthew S, Ressler Kerry J, Risbrough Victoria B, Rothbaum Barbara O, Roy-Byrne Peter, Seedat Soraya, Smith Alicia K, Stevens Jennifer S, van den Heuvel Leigh Luella, Voisey Joanne, Young Ross McD, Zoellner Lori A, Nievergelt Caroline M, Wolf Erika J
Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Psychiatry, University of California, San Diego, San Diego, CA, United States.
Front Neurosci. 2021 Jun 23;15:678503. doi: 10.3389/fnins.2021.678503. eCollection 2021.
Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European ( = 70,870) and African ( = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, < 1E-20; DBP: β = 1.32, SE = 0.04, < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.
越来越多的研究表明,创伤后应激障碍(PTSD)可能是心血管健康状况不佳的一个风险因素,然而,我们对于谁在创伤后发生不良心血管结局的风险可能最大的了解仍然有限。在本研究中,我们首次考察了PTSD症状和血压遗传学对连续血压水平的个体及协同作用。我们利用了精神基因组学联盟-PTSD身体健康工作组的力量,并在涉及72224名有欧洲(n = 70870)和非洲(n = 1354)血统的创伤暴露个体的11项研究中调查了这些关联。通过收缩压(SBP)和舒张压(DBP)的多基因评分(PGS)对血压的遗传贡献进行建模,这些评分来自先前的跨种族血压全基因组关联研究(GWAS)。跨种族荟萃分析的结果显示,PGS对血压水平有显著的主效应[SBP:β = 2.83,标准误(SE)= 0.06,P < 1E - 20;DBP:β = 1.32,SE = 0.04,P < 1E - 20]。跨种族荟萃分析中还检测到PTSD症状对SBP和DBP有显著的主效应,不过这些结果存在显著的异质性。当纳入贡献最大的研究——英国生物银行的数据时,PTSD症状与SBP水平呈负相关(β = -1.46,SE = 0.44,P = 9.8E - 4),与DBP水平呈正相关(β = 0.70,SE = 0.26,P = 8.1E - 3)。然而,在跨种族荟萃分析中排除英国生物银行队列后,PTSD症状与SBP水平之间存在名义上显著的正相关(β = 2.81,SE = 1.13,P = 0.01);未观察到DBP有显著关联(β = 0.43,SE = 0.78,P = 0.58)。在荟萃分析中,血压PGS并未显著调节PTSD症状与血压水平之间的关联。需要进一步的研究来更好地了解PTSD与高血压相关的程度,以及遗传和背景因素在影响心血管风险方面可能发挥的作用。