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Dissecting Biological Pathways of Psychopathology using Cognitive Genomics

By Max Lam, Chia-Yen Chen, W. David Hill, Charley Xia, Ruoyu Tian, Daniel F Levey, Joel Gelernter, Murray B Stein, Biogen Biobank Team, Alexander S. Hatoum, Hailiang Huang, Anil K. Maholtra, Heiko Runz, Tian Ge, Todd Lencz

Posted 23 Jul 2021
medRxiv DOI: 10.1101/2021.07.20.21260487

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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