Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology
Max Lam, Chia‐Yen Chen, W. David Hill, Charley Xia, Ruoyu Tian, Daniel F. Levey, Joel Gelernter, Murray B. Stein, Alexander S. Hatoum, Hailiang Huang, Anil K. Malhotra, Heiko Runz, Tian Ge, Todd Lencz
Abstract
Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call "meta-loci", showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant meta-loci. Further, we demonstrate that neurodevelopmental gene sets are dissociable across CTP meta-loci with respect to their spatial distribution across the brain. Additionally, we find that GABA-ergic, cholinergic, and glutamatergic genes drive pleiotropic relationships within dissociable meta-loci.