Gene-based and pathway analyses using MAGMA26 yielded no significant results after correction for multiple testing, consistent with observation from other GWAS analyses in which gene and pathway methods did not yield significant findings until the primary GWAS was well powered enough to identify specific risk loci. Nevertheless, we present the top gene and pathway results in Supplementary Tables S7 and S8. Top results for genes did not include PTSD candidate genes, though GRINA, a glutamate receptor, was among the top 20 results. The top pathway was the neurotrophic factor-mediated Trk receptor signaling pathway,36 which includes BDNF (brain-derived neurotrophic factor), NGF (nerve growth factor) and other neurotrophin-related genes, that collectively regulate synaptic strength and plasticity in the nervous system of mammals.37 Given the primacy of learning in the PTSD phenotype, this is an intriguing pathway result that awaits follow-up in a better-powered analysis.
