Integration of Metabolomic and Brain Imaging Data Highlights Pleiotropy Among Posttraumatic Stress Disorder, Glycoprotein Acetyls, and Pallidum Structure

• DOI: 10.1016/j.bpsgos.2025.100482
• Publication Date: 2025-03-17T19:20:45Z
• Authors: Solveig Løkhammer; Markos Tesfaye; Brenda Cabrera-Me...; Kristoffer Sandås; Gita A. Pathak; Eleni Friligkou; Stéphanie Le Hellard; Renato Polimanti
• Keywords: Pleiotropy

The development of posttraumatic stress disorder (PTSD) is attributable to the interplay between exposure severe traumatic events, environmental factors, and biological characteristics. Blood brain imaging markers have been associated with PTSD. However, our knowledge, no study has systematically investigated genetic relationship PTSD, metabolic biomarkers, brainwide imaging. We integrated genome-wide data informative 233 3935 imaging-derived phenotypes (IDPs). Pleiotropy was assessed by applying global local correlation, colocalization, genetically inferred causality. observed significant overlap PTSD glycoprotein acetyls (GlycA) (a stable inflammatory biomarker) in 2 independent cohorts (discovery r g = 0.26, p 1.00 × 10-4; replication 0.23, 5.99 10-19). Interestingly, there correlation anxiety GlycA (p .33). were both correlated median T2∗ left pallidum (IDP-1444: 0.14, 1.39 10-5; -0.38, 2.50 10-3, respectively). Local 7 regions < 2.0 10-5), mapping genes related immune response, inflammation, processes. Furthermore, we identified 1 variant, rs12048743, evidence horizontal pleiotropy linking IDP-1444 (z 17.14, z -6.07, theta 2.06 10-8). Regional colocalization among GlycA, IDP-1444, tissue-specific transcriptomic regulation for frontal cortex testis (rs12048743-chr1q32.1; posterior probability > 0.8). While also tested causality metabolomic IDPs, these not consistent across different informed causal inference methods. Our findings highlight a new putative pleiotropic mechanism that links systemic inflammation structure