[Genetic variants associated with the development of stress disorders: A systematic review of GWAS]

Abstract

Studying the genetic basis of post-traumatic stress disorder (PTSD) can be useful in predicting its risk in a person with a history of severe traumatic stress and in facilitating earlier diagnosis and referral to a specialist. The aim of the study is to review all GWAS studies related to PTSD. In total, 20 studies were included, of which 5 meta-analyses and 9 included war veterans. The functions of genes and their associations were considered, which included single-cell polymorphisms in different groups of genes involved in embryogenesis, neuron formation, and cell functioning, as well as many DNA sequences with non-coding RNA transcribed. The repeatability of the results between studies and replicative samples was studied. Between the studies, the associations were repeated in the CAMKV, CDHR4, DCC, FAM120A, FOXP2 (3 studies), MAD1L1 (3 studies), MAPT, NCAM1, NOS1, SP4, ZMYM4, TCF4 genes. A new large-scale study with many found associations was considered individually. Studies regarding polygenic risk were also studied, and several studies showed genetic comorbidity with anxiety and bipolar disorder. However, the models developed by the authors explain a small percentage of variance and are weakly repeated in other samples. It may be possible to solve this problem by using larger samples and clearer homogeneous inclusion criteria. Thus, at the moment, there are few GWAS studies of PTSD; they are ambiguous and uninformative compared to the same studies for other mental disorders, but they have further potential for assessing the risks of developing the disease.

Keywords: GWAS; PTSD; polygenic risk; stress.