Carvalho, C.MWendt, F.RStein, D.JStein, M.BGelernter, JBelangero, S.IPolimanti, R2024-07-292024-07-292019-11-30Carvalho CM, Wendt FR, Stein DJ, Stein MB, Gelernter J, Belangero SI, Polimanti R. Investigating Causality Between Blood Metabolites and Emotional and Behavioral Responses to Traumatic Stress: a Mendelian Randomization Study. Mol Neurobiol. 2020 Mar;57(3):1542-1552. doi: 10.1007/s12035-019-01823-2.10.1007/s12035-019-01823-2https://pubmed.ncbi.nlm.nih.gov/31786776/https://doi.org/10.1007/s12035-019-01823-2https://hdl.handle.net/11288/597040To investigate the causal relationship between blood metabolites and traits related to trauma-response, we combined genome-wide and metabolome-wide datasets generated from large-scale cohorts. Five trauma-response traits ascertained in the UK Biobank (52,816 < N < 117,900 individuals) were considered: (i) "Avoided activities/situations because of previous stressful experience" (Avoidance); (ii) "Felt distant from other people" (Distant); (iii) "Felt irritable/had angry outbursts" (Irritable); (iv) "Felt very upset when reminded of stressful experience" (Upset); (v) "Repeated disturbing thoughts of stressful experience". These were investigated with respect to 52 blood metabolites tested in a previous genome-wide-association study (N = 24,925 European-ancestry individuals). Linkage disequilibrium score regression, polygenic risk scoring (PRS), and Mendelian randomization were applied to the datasets. We observed that 14 metabolites were genetically correlated with trauma-response traits (p < 0.05). High-resolution PRS of 4 metabolites (citrate; glycoprotein acetyls; concentration of large very-low-density lipoproteins (VLDL) particles (LVLDLP); total cholesterol in medium particles of VLDL (MVLDLC)) were associated with trauma-response traits (false discovery rate Q < 10%). These genetic associations were partially due to causal relationships (Citrate→Upset β = - 0.058, p = 9.1 × 10-4; Glycoproteins→Avoidance β = 0.008, p = 0.003; LVLDLP→Distant β = 0.008, p = 0.022; MVLDLC→Avoidance β = 0.019, p = 3 × 10-4). No reverse associations were observed. In conclusion, our study supports causal relationships between certain blood metabolites and emotional and behavioral responses to traumatic experiences.enAttribution 3.0 United Stateshttp://creativecommons.org/licenses/by/3.0/us/Blood metabolitesMendelian randomizationTrauma responseTraumatic stressArticleMolecular Neurobiology