Genetic relationships between eight psychiatric disorders.A) SNP-based genetic correlations (rg) were estimated between eight neuropsychiatric disorders using LDSC. The size of the circles scales with the significance of the p-values. The darker the color, the larger the magnitude of rg. Star sign (*) indicates statistical significance after Bonferroni correction. (B) SNP-based genetic correlations between eight disorders were depicted using an in-directed graph to reveal complex genetic relationships. Only significant genetic correlations after Bonferroni correction in (A) were displayed. Each node represents a disorder, with edges indicating the strength of the pairwise correlations. The width of the edges increases, while the length decreases, with the absolute values of rg. (C) Based on the results of an exploratory factor analysis of the genetic correlation matrix produced from multivariable LD-score regression, a confirmatory factor model with three correlated genetic factors was specified using Genomic SEM and estimated with the weighted least squares algorithm. In this solution, each common genetic factor (i.e., F1g, F2g, F3g) represents variation in genetic liability that is shared across the disorders that load on it. These common factors are specified so as to account for the genetic covariation among the psychiatric disorders. For example, F1g represents shared genetic liability among disorders characterized by compulsive behaviors (AN, OCD and TS). One-headed arrows connecting the common genetic factors to the individual disorders represent standardized loadings, which can be interpreted as coefficients from a regression of the true genetic liability for the disorder on the common factor. Two-headed arrows connecting the three factors to one another represent their correlations. Two-headed arrows connecting the genetic components of the individual psychiatric disorders to themselves represent residual genetic variances and correspond to the proportion of heritable variation in liability to each individual psychiatric disorder that is unexplained by the three factors. Standardized parameters are depicted with their standard errors in parentheses. Paths labeled 1 with no standard errors reported are fixed parameters, which are used for scaling.
