The interaction of early life factors and depression-associated loci affecting the age at onset of the depression

Multiple previous studies explored the associations between early life factors and the age at onset of the depression. However, they only focused on the influence of environmental or genetic factors, without considering the interactions between them. Based on previous genome-wide association study (GWAS) data, we first calculated polygenic risk score (PRS) for depression. Regression analyses were conducted to assess the interacting effects of depression PRS and 5 early life factors, including felt hated by family member (N = 40,112), physically abused by family (N = 40,464), felt loved (N = 35633), and sexually molested (N = 41,595) in childhood and maternal smoking during pregnancy (N = 38,309), on the age at onset of the depression. Genome-wide environment interaction studies (GWEIS) were then performed to identify the genes interacting with early life factors for the age at onset of the depression. In regression analyses, we observed significant interacting effects of felt loved as a child and depression PRS on the age at onset of depression in total sample (β = 0.708, P = 5.03 × 10(−3)) and males (β = 1.421, P = 7.64 × 10(−4)). GWEIS identified a novel candidate loci interacting with felt loved as a child at GSAP (rs2068031, P = 4.24 × 10(–8)) and detected several genes with suggestive significance association, such as CMYA5 (rs7343, P = 2.03 × 10(–6)) and KIRREL3 (rs535603, P = 4.84 × 10(–6)) in males. Our results indicate emotional care in childhood may affect the age at onset of depression, especially in males, and GSAP plays an important role in their interaction.