038_ Genetic contributions to transdiagnostic symptom dimensions in patients with major depressive disorder, bipolar disorder, schizoaffective disorder, and schizophrenia
Research Question and Aims
In clinical practice, major depressive disorder, bipolar disorder, and schizophrenia are treated as distinct diagnostic categories despite a considerable degree of phenotypic and genetic overlap (e.g., Lee et al. 2019). Factor analyses of psychopathological symptoms have identified underlying transdiagnostic symptom dimensions, supporting the notion of shared etiological factors. Recently, Stein et al. (2020) have described a 5-factor model of psychopathological symptoms in a large group of psychiatric patients from the FOR2107 cohort (Kircher et al. 2019). To follow up on genetic contributions, the genetic associations with each of the 5 factor dimensions have been investigated within the FOR2107 cohort (unpublished data). In the here proposed analysis, selected associations are sought to be replicated in the independent PsyCourse cohort.
Replication analyses of selected genetic associations with the transdiagnostic symptom dimensions will be conducted in individuals of the PsyCourse study that were diagnosed with major depressive disorder, bipolar disorder, schizophrenia, or schizoaffective disorder. The factor dimensions as quantitative phenotypes will be remodeled using relevant items of symptom rating scales collected in the PsyCourse study such as PANSS and YMRS. For selected genetic markers, associations with the quantitative phenotypes will be examined using the linear regression approach in PLINK 1.90 including sex, age, and relevant ancestry components as covariates. Subsequently, association results will be meta-analyzed with results from the discovery cohort using METAL.
Phenotypic data ("200715_v4.1_psycourse_wd.RData"):
If available (no variable found in codebook):
Age of onset
Number of psychotic episodes
Remission status (acute vs. remitted)
Biological analysis data:
Imputed genome-wide genotype data
Ancestry components (from MDS or PCA) if available