Genome-wide association studies of stress score in a Korean Cohort

Despite ongoing research on factors affecting stress, there is a shortage of research on genetic variation using single nucleotide polymorphisms (SNPs). Thus, this study aims to identify genes that may affect the risk of stress in a large-scale Korean cohort. The stress survey used in this study consisted of 40 questions, organized into the following four categories: 10 questions on General Stress (GenST); 10 questions on Mental Stress (MenST); 10 questions on Physical Stress (PhyST); and 10 questions on Activity Stress (ActST). An overall stress score was calculated as the sum of the survey scores from each category, with a high stress score defined as a stress score in which the proportion of insomnia was large. Genome-wide association studies of approximately 320,000 SNPs acquired from the Korea Centers for Disease Control and Prevention (KCDC) were conducted to explore the risk of stress in the four categories. As a result, three loci were identified for GenST, no significant loci were observed for MenST, four loci were identified for PhyST, and two loci were identified for ActST. The most significant SNP of GenST (rs9353437) was located in an epidermal growth factor gene (eyes shut homolog, EYS) and expressed in the photoreceptor layer of the retina. The genome-wide association studies' (GWAS) results of PhyST showed a significant SNP (rs4924370) in a spliceosomal factor (Aquarius intron-binding spliceosomal factor, AQR). Notably, the second most significant SNP (rs1991002) was located in an oxidoreductase gene (NADH:Ubiquinone Oxidoreductase Subunit S4, NDUFS4) and was also marginally associated with GenST, MenST, and ActST (p-value < 0.05). A bioinformatics analysis of the genes linked to the identified SNPs demonstrated the presence of many genes that could be associated with neurotransmission or stress. Although the stress survey or classification criteria for stress scores used in this study were ambiguous, such results may be the first to expand upon the understanding of the genetic variations and the molecular mechanisms that may cause vulnerabilities to stress.