Contribution of common genetic variants to disease status and symptom dimensions in affective and psychotic disorders

Abstract

Affective and psychotic disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorders (SSD), represent complex psychiatric conditions with a moderate to high heritability. Throughout the last decade, genome-wide association studies (GWAS) have demonstrated the association of many common genetic variants with disease risk. However, the pathophysiological mechanisms of affective and psychotic disorders are still incompletely understood and it is expected that many more disease-associated genetic loci await identification. Moreover, while the different affective and psychotic disorders are considered distinct entities by current diagnostic systems, they exhibit notable phenotypic overlaps and substantial genetic correlations. This suggests that etiological processes may be partially shared between diagnostic groups. Against this backdrop, the three studies included in this thesis were conducted to improve our understanding of the role of common genetic variation in affective and psychotic disorders. In particular, in the first and second study, the contribution of common genetic variants to symptom dimensions of acute and lifetime psychopathology observed across MDD, BD, and SSD was examined. In the third study, the largest GWAS meta-analysis of BD to date was conducted, which revealed novel disease-associated loci and provided insights into the underlying pathobiology via a plethora of GWAS downstream analyses. Altogether, the results of this research expand our knowledge on the complex relationships of common genetic variants with disease status and symptom dimensions within and across affective and psychotic disorders.