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Distributed genetic architecture across the hippocampal formation implies common neuropathology across brain disorders

Author

Listed:
  • Shahram Bahrami

    (University of Oslo)

  • Kaja Nordengen

    (University of Oslo
    Oslo University Hospital)

  • Alexey A. Shadrin

    (University of Oslo
    University of Oslo)

  • Oleksandr Frei

    (University of Oslo
    University of Oslo)

  • Dennis Meer

    (University of Oslo
    Maastricht University)

  • Anders M. Dale

    (University of California
    University of California San Diego
    University of California at San Diego)

  • Lars T. Westlye

    (University of Oslo
    University of Oslo
    University of Oslo)

  • Ole A. Andreassen

    (University of Oslo
    University of Oslo)

  • Tobias Kaufmann

    (University of Oslo
    University of Tübingen)

Abstract

Despite its major role in complex human functions across the lifespan, most notably navigation, learning and memory, much of the genetic architecture of the hippocampal formation is currently unexplored. Here, through multivariate genome-wide association analysis in volumetric data from 35,411 white British individuals, we reveal 177 unique genetic loci with distributed associations across the hippocampal formation. We identify genetic overlap with eight brain disorders with typical onset at different stages of life, where common genes suggest partly age- and disorder-independent mechanisms underlying hippocampal pathology.

Suggested Citation

  • Shahram Bahrami & Kaja Nordengen & Alexey A. Shadrin & Oleksandr Frei & Dennis Meer & Anders M. Dale & Lars T. Westlye & Ole A. Andreassen & Tobias Kaufmann, 2022. "Distributed genetic architecture across the hippocampal formation implies common neuropathology across brain disorders," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31086-w
    DOI: 10.1038/s41467-022-31086-w
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    References listed on IDEAS

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    1. Dennis Meer & Oleksandr Frei & Tobias Kaufmann & Alexey A. Shadrin & Anna Devor & Olav B. Smeland & Wesley K. Thompson & Chun Chieh Fan & Dominic Holland & Lars T. Westlye & Ole A. Andreassen & Anders, 2020. "Understanding the genetic determinants of the brain with MOSTest," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    2. Edward H. Liao & Wesley Hung & Benjamin Abrams & Mei Zhen, 2004. "An SCF-like ubiquitin ligase complex that controls presynaptic differentiation," Nature, Nature, vol. 430(6997), pages 345-350, July.
    3. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    4. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    5. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    6. Yi Nong & Yue-Qiao Huang & William Ju & Lorraine V. Kalia & Gholamreza Ahmadian & Yu Tian Wang & Michael W. Salter, 2003. "Glycine binding primes NMDA receptor internalization," Nature, Nature, vol. 422(6929), pages 302-307, March.
    7. Derrek P. Hibar & Hieab H. H. Adams & Neda Jahanshad & Ganesh Chauhan & Jason L. Stein & Edith Hofer & Miguel E. Renteria & Joshua C. Bis & Alejandro Arias-Vasquez & M. Kamran Ikram & Sylvane Desriviè, 2017. "Novel genetic loci associated with hippocampal volume," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    8. Dennis Meer & Oleksandr Frei & Tobias Kaufmann & Alexey A. Shadrin & Anna Devor & Olav B. Smeland & Wesley K. Thompson & Chun Chieh Fan & Dominic Holland & Lars T. Westlye & Ole A. Andreassen & Anders, 2020. "Author Correction: Understanding the genetic determinants of the brain with MOSTest," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
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