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Publication: Investigating causality between blood metabolites and emotional and behavioral responses to traumatic stress: A mendelian randomization study
Carvalho, C.M Wendt, F.R Stein, D.J Stein, M.B Gelernter, J Belangero, S.I Polimanti, R
Carvalho, C.M
Wendt, F.R
Stein, D.J
Stein, M.B
Gelernter, J
Belangero, S.I
Polimanti, R
Abstract
To 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.
Description
Date
2019-11-30
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Publisher
Springer Nature
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Keywords
Blood metabolites,Mendelian randomization,Trauma response,Traumatic stress
Citation
Carvalho 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.