Dissecting Biological Pathways of Psychopathology using Cognitive Genomics
Lam, M.; Chen, C.-Y.; Hill, W. D.; Xia, C.; Tian, R.; Levey, D. F.; Gelernter, J.; Stein, M. B.; Biogen Biobank Team, ; Hatoum, A. S.; Huang, H.; Maholtra, A. K.; Runz, H.; Ge, T.; Lencz, T.
Show 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 identified collective segments of the genome, which we call "meta-loci", that showed differential pleiotropic patterns for psychopathology relative to either General Cognitive Ability (GCA) or Non-Cognitive Skills (NCS). We observed that neurodevelopmental gene sets expressed during the prenatal-early childhood predominated in GCA-relevant meta-loci, while post-natal synaptic gene sets were more involved in NCS-relevant meta-loci. Notably, we found that GABA-ergic, cholinergic, and glutamatergic genes drove pleiotropic relationships within dissociable NCS meta-loci.
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