International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations

“…We report 19 metabolite-phenotype associations that were identified at a false discovery rate (FDR) cutoff of 0.05 (Table 1, Supplementary Table 10, Supplementary Figure 26). The phenotypes (and significantly associated metabolites) were schizophrenia 32 31 (unknown metabolite X-24295), and attention deficit hyperactivity disorder (ADHD) 24 (orotate and malate). A two-sample MR analysis was performed for the 19 significant metabolite-phenotype associations.…”

A decennial review of psychotraumatology: what did we learn and where are we going?

“…Largescale molecular platforms, such as those involved with genome-wide association studies (GWAS) allow for the examination of millions of variants in association with traits, and afford an agnostic approach to discover genes and biologic systems involved with disorders. The most recent meta-analyses of GWAS data from the PGC PTSD workgroup (n~200,000) revealed numerous significant variants and quantified the molecular heritability of PTSD (Nievergelt et al, 2019). Collaborative efforts from the PGC have led to progress on finding epigenome-wide significant sites related to risk for PTSD (Smith et al, 2019).…”

An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci

“…Genetic studies of posttraumatic stress disorder (PTSD) diatheses conducted to date have focused primarily on identifying DNA variants (e.g., single-nucleotide polymorphisms, SNPs) that confer risk for the development of the disorder through candidate gene or genome-wide association studies (GWASs; see, e.g., [1,2]). More recently, studies have also examined differences between PTSD cases and controls in patterns of gene expression [3] and/or DNA methylation (DNAm [4][5][6];).…”