Heritability estimates of individual psychological distress symptoms from genetic variation

Background: Psychological distress symptoms are associated with an increased risk of psychiatric disorders and medical illness. Although psychological distress is influenced by environmental factors, such as socioeconomic status, lifetime events, or interpersonal relationships, substantial interindividual variation also exists. However, heritability and genetic determinants of distress are poorly understood. Methods: In the Korean Genome and Epidemiology Study sample (n = 12,680), we estimated the heritability of individual psychological distress symptoms using the GCTA-REML method and carried out a genome-wide association study of individual psychological distress symptoms showing significant heritability. Results: We found three psychological distress items showing significant heritability: subjective well-being (9%), fatigue and appetite (11%), and enjoying daily life (8%). Additionally, we found genome-wide significant associations of rs6735649 located between STEAP3 and C1QL2 on chromosome 2 with subjective well-being (P = 1.32 x 10(-8), odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.12 -1.25) and rs35543418 located between SYT16 and KCNH5 on chromosome 14 with enjoying daily life (P = 1.33 x 10(-8), OR = 1.59, 95% CI: 1.35 -1.86). Limitations: The lack of replication in independent cohorts and longitudinal assessment of distress may limit generalizability. Conclusions: Our results indicate that distress symptoms are partly heritable. Further analysis in larger cohorts investigating gene-environment interactions is required to identify genetic variants that explain the proportion of variation in distress.

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