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Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology

Author

Listed:
  • Max Lam

    (The Zucker Hillside Hospital, Northwell
    Feinstein Institutes for Medical Research
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Chia-Yen Chen

    (Translational Biology, Research and Development, Biogen Inc)

  • W. David Hill

    (University of Edinburgh)

  • Charley Xia

    (University of Edinburgh)

  • Ruoyu Tian

    (Computational Biology and Human Genetics, Dewpoint Therapeutics)

  • Daniel F. Levey

    (Yale University School of Medicine
    VA Connecticut Healthcare System)

  • Joel Gelernter

    (Yale University School of Medicine
    VA Connecticut Healthcare System
    Yale University School of Medicine
    Yale University School of Medicine)

  • Murray B. Stein

    (VA San Diego Healthcare System
    University of California, San Diego
    University of California San Diego)

  • Alexander S. Hatoum

    (Washington University in St. Louis Medical School)

  • Hailiang Huang

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Anil K. Malhotra

    (The Zucker Hillside Hospital, Northwell
    Feinstein Institutes for Medical Research
    Zucker School of Medicine at Hofstra/Norwell
    Zucker School of Medicine at Hofstra/Norwell)

  • Heiko Runz

    (Translational Biology, Research and Development, Biogen Inc)

  • Tian Ge

    (Broad Institute of MIT and Harvard
    Center for Genomic Medicine, Massachusetts General Hospital
    Massachusetts General Hospital, Harvard Medical School)

  • Todd Lencz

    (The Zucker Hillside Hospital, Northwell
    Feinstein Institutes for Medical Research
    Zucker School of Medicine at Hofstra/Norwell
    Zucker School of Medicine at Hofstra/Norwell)

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.

Suggested Citation

  • 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, 2022. "Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34418-y
    DOI: 10.1038/s41467-022-34418-y
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