Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology
Year: 2021
Type: article
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.
Source: European Neuropsychopharmacology
Authors: 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. Malhotra, Heiko Runz, Tian Ge, Todd Lencz
Institutions: Broad Institute, Feinstein Institute for Medical Research, Massachusetts General Hospital, Institute of Mental Health, Zucker Hillside Hospital, Stanley Center for Psychiatric Research, Biogen (United States), Hofstra University, University of Edinburgh, Yale University, VA Connecticut Healthcare System, University of California San Diego, VA San Diego Healthcare System, University of Colorado Boulder, University of Washington, Washington University in St. Louis, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Harvard University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Awards: G5373111116, Exploring the genetic basis of AD progression, From genetic sequence to phenotypic consequence: Genetic and environmental links between cognitive ability, socioeconomic position, and health, Cognitive Genomics as a Window on Neurodevelopment and Psychopathology, Mass Multivariate Derivation and Validation of AUD Biotypes using Developmental Imaging and Genomic Approaches, Yale Clinical and Translational Science Award
OpenAlex ID: W3204902805