Dissecting the genetic association of C-reactive protein with PTSD, traumatic events, and social support

Author(s):Show less -

Carvalho, Carolina Muniz ^{[1, 2, 3, 4]} ; Wendt, Frank R. ^{[1, 2]} ; Maihofer, Adam X. ^{[5, 6]} ; Stein, Dan J. ^[7] ; Stein, Murray B. ^{[8, 5]} ; Sumner, Jennifer A. ^[9] ; Hemmings, Sian M. J. ^[10] ; Nievergelt, Caroline M. ^{[5, 6]} ; Koenen, Karestan C. ^[11] ; Gelernter, Joel ^{[12, 13, 1, 2]} ; Belangero, I, Sintia ; Polimanti, Renato ^{[1, 2]}

Affiliation:Show less -

^[1] Yale Sch Med, Dept Psychiat, West Haven, CT 06516 - USA

^[2] VA CT Healthcare Ctr, West Haven, CT 06516 - USA

^[3] I, Univ Fed Sao Paulo UNIFESP, Dept Psychiat, Sao Paulo, SP - Brazil

^[4] I, Univ Fed Sao Paulo UNIFESP, Dept Morphol & Genet, Genet Div, Sao Paulo, SP - Brazil

^[5] Univ Calif San Diego, Sch Med, Dept Psychol, La Jolla, CA 92093 - USA

^[6] Vet Affairs San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA - USA

^[7] Univ Cape Town, Dept Psychiat & Neurosci Inst, MRC Unit Risk & Resilience Mental Disorders, Cape Town - South Africa

^[8] Vet Affairs San Diego Healthcare Syst, Psychiat Serv, San Diego, CA - USA

^[9] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA - USA

^[10] Stellenbosch Univ, Fac Med & Hlth Sci, Dept Psychiat, Cape Town - South Africa

^[11] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA - USA

^[12] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 - USA

^[13] Yale Univ, Sch Med, Dept Neurosci, New Haven, CT 06510 - USA

• Document type: Journal article
• Source: NEUROPSYCHOPHARMACOLOGY; v. 46, n. 6 MAR 2020.
• Web of Science Citations: 2

Abstract

Inflammatory markers like C-reactive protein (CRP) have been associated with post-traumatic stress disorder (PTSD) and traumatic experiences, but the underlying mechanisms are unclear. We investigated the relationship among serum CRP, PTSD, and traits related to traumatic events and social support using genetic association data from the Psychiatric Genomics Consortium (23,185 PTSD cases and 151,309 controls), the UK Biobank (UKB; up to 117,900 individuals), and the CHARGE study (Cohorts for Heart and Aging Research in Genomic Epidemiology, 148,164 individual). Linkage disequilibrium score regression, polygenic risk scoring, and two-sample Mendelian randomization (MR) analyses were used to investigate genetic overlap and causal relationships. Genetic correlations of CRP were observed with PTSD (rg = 0.16, p = 0.026) and traits related to traumatic events, and the presence of social support (-0.28 < rg < 0.20; p < 0.008). We observed a bidirectional association between CRP and PTSD (CRP -> PTSD: beta = 0.065, p = 0.015; PTSD -> CRP: beta = 0.008, p = 0.009). CRP also showed a negative association with the ``felt loved as a child{''} trait (UKB, beta = -0.017, p = 0.008). Owing to the known association of socioeconomic status (SES) on PTSD, a multivariable MR was performed to investigate SES as potential mediator. We found that household income (univariate MR: beta = -0.22, p = 1.57 x 10(-7); multivariate MR: beta = -0.17, p = 0.005) and deprivation index (univariate MR: beta = 0.38, p = 1.63 x 10(-9); multivariate MR: beta = 0.27, p = 0.016) were driving the causal estimates of ``felt loved as a child{''} and CRP on PTSD. The present findings highlight a bidirectional genetic association between PTSD and CRP, also suggesting a potential role of SES in the interplay between childhood support and inflammatory processes with respect to PTSD risk. (AU)

• FAPESP's process: 18/05995-4 - Dissecting the causal role of anthropometric traits in the risk of posttraumatic stress disorder in women
• Grantee: Carolina Muniz Felix de Carvalho
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate