Depression polygenic scores are associated with major depressive disorder diagnosis and depressive episode in Mexican adolescents

Abstract

Objective. Large-scale genome-wide association studies have uncovered genetic variants associated with depression; however, most of this work has been limited to adults of European ancestry. We investigate the ability of depression polygenic risk scores (PRS) to predict both lifetime and past year major depressive disorder (MDD) diagnosis and the experience of a major depressive episode (MDE) in a sample of adolescents with admixed ancestry from Mexico City, and explore whether adverse life events moderate these relations. Methods. The study sample consisted of adolescents (N=1,152) aged 12-17 from Mexico City who were interviewed and genotyped as part of a general population survey on adolescent mental health. PRS for depression were derived using summary statistics from a large-scale discovery genome-wide association study (GWAS) conducted on depressive symptoms that included over 800,000 individuals of European ancestry (Howard et al., 2019). Results. Higher depression PRS were associated with a higher likelihood of both past year MDD and MDE and lifetime MDE, accounting for 1.5%-2.5% of the variance in these outcomes. Adversity did not moderate the relationship between depression PRS and lifetime or past year MDD or MDE. Limitations. This study is cross-sectional. As such, a few participants might have experience MDD/MDE after the interview. In addition, our sample comprised only Mexican youth and thus it may not generalize to other populations. Conclusions. Our results indicate that depression PRS derived from a European ancestry GWAS are associated with MDD and MDE risk among Mexican adolescents and have the potential to aid in the identification of youth who may be genetically prone to developing depressive symptoms.