Environmental and genome-wide association study on children anxiety and depression

Abstract

Anxiety and Depression are currently among the most common mental disorders in children and adolescents. Both genetics and environments play an important role in the development and progress of disorders. This study aimed to understand the effect of multiscale environmental factors on anxiety and depression in school-age children, to refine the identification of genetic variants contributing to susceptibility to anxiety and depression, and to evaluate the genetic heritability. We analyzed data from the Adolescent Brain and Cognitive Development study and computed one principal factor to present the overall anxiety and depression scale in 11,875 participants with ages between 9 and 10 years old. Linear mixed-effect models along with the recursive feature elimination regression and LASSO regression models were used to determine the environmental effects from the macro scale (population density, air pollution), meso scale (neighborhood, school), to micro scale (family and individual experience). Genome-wide association analyses were then performed controlling for environmental factors and sample relatedness to determine the susceptible genetic variants. Furthermore, heritability was calculated for the white population. The results showed that six environmental factors (early life stress, household income, population density, area crime, neighborhood safety, and school risk) and sex had significant effect on anxiety/depression score. Genome-wide association tests showed no SNPs reached a genome-wide significance (p=5e-08), but some genetic mutations including SNPs in SCN1A showed promising effects, and the heritability was estimated close to 15% in the white population.