Fig. 2: Genome-wide by environment interaction results of cumulative childhood maltreatment experiences in UK Biobank.
We conducted a genome-wide by environment interaction analysis with cumulative childhood maltreatment (CM) experiences to search for genetic variants associations with major depressive disorder (MDD) using the SaddlePoint Approximation implementation of Gene-by-Environment (G-by-E) analysis (SPAGE) approach in UK Biobank (Ncases = 26,664, Ncontrols = 85,715). a Shown is G-by-E interaction P values versus chromosomal position. We identified one locus at genome-wide significance (two-tailed genome-wide corrected threshold at P < 5×10 − 8; red dashed horizontal line). The arrow indicates the index variant IDO2 rs7846217. The orange dashed line indicates genome-wide suggestive significant threshold P < 1e-05. Source data are provided through Figshare (https://doi.org/10.6084/m9.figshare.27124452). b Shown is odds ratios (ORs) of different types of CM on risk for MDD using logistic regression, stratified by IDO2 rs7846217 genotypes (three genotypes: CC, CT, and TT). The center of each dot represents the OR, with error bars indicating the 95% confidence intervals (CIs). For CM (yes/no, indicating binary CM experience), the ORs reflect the risk for MDD in individuals exposed to CM refer to those unexposed. For cumulative CM (Cum-CM), physical abuse (PhyAbu), emotional abuse (EmoAbu), sexual abuse (SexAbu), physical neglect (PhyNeg), and emotional neglect (EmoNeg), the ORs represent the odds of MDD risk per 1 standard deviation (SD) increase in the respective CM severity scale. Two-tailed P values for the G-by-E interaction effects are shown below the x-axis. Source data are provided as a Source Data file. c Shown is odds ratios (ORs) of IDO2 rs7846217 TT genotype refer to TC/CC genotype on risk for MDD, stratified by CM exposure. The center of each dot represents the OR, with error bars indicating the 95% CIs. Two-tailed P values are shown below the x-axis.
