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William N, Reissner C, Sargent R, et al. Neurexin 1 variants as risk factors for suicide death. Mol Psychiatry. 2021;doi: 10.1038/s41380-021-01190-2.
William, N., Reissner, C., Sargent, R., Darlington, T. M., DiBlasi, E., Li, Q. S., Keeshin, B., Callor, W. B., Ferris, E., Jerominski, L., Smith, K. R., Christensen, E. D., Gray, D. M., Camp, N. J., Missler, M., Williams, M. E., & Coon, H. (2021). Neurexin 1 variants as risk factors for suicide death. Molecular psychiatry, . https://doi.org/10.1038/s41380-021-01190-2
William, Nancy, et al. "Neurexin 1 variants as risk factors for suicide death." Molecular psychiatry vol. (2021). doi: https://doi.org/10.1038/s41380-021-01190-2
William N, Reissner C, Sargent R, Darlington TM, DiBlasi E, Li QS, Keeshin B, Callor WB, Ferris E, Jerominski L, Smith KR, Christensen ED, Gray DM, Camp NJ, Missler M, Williams ME, Coon H. Neurexin 1 variants as risk factors for suicide death. Mol Psychiatry. 2021 Jun 25; doi: 10.1038/s41380-021-01190-2. Epub 2021 Jun 25. PMID: 34168285; PMCID: PMC8709873.
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Mol Psychiatry. 2021 Jun 25; doi: 10.1038/s41380-021-01190-2. Epub 2021 Jun 25.

Neurexin 1 variants as risk factors for suicide death.

Molecular psychiatry

Nancy William, Carsten Reissner, Robert Sargent, Todd M Darlington, Emily DiBlasi, Qingqin S Li, Brooks Keeshin, William B Callor, Elliott Ferris, Leslie Jerominski, Ken R Smith, Erik D Christensen, Douglas M Gray, Nicola J Camp, Markus Missler, Megan E Williams, Hilary Coon

Affiliations

  1. Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.
  2. Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, Münster, Germany.
  3. Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  4. Department of Psychology, University of Oregon, Eugene, OR, USA.
  5. Neuroscience, Janssen Research & Development, LLC, Titusville, NJ, USA.
  6. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
  7. Utah State Office of the Medical Examiner, Utah Department of Health, Salt Lake City, UT, USA.
  8. Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, UT, USA.
  9. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
  10. Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA. [email protected].

PMID: 34168285 PMCID: PMC8709873 DOI: 10.1038/s41380-021-01190-2

Abstract

Suicide is a significant public health concern with complex etiology. Although the genetic component of suicide is well established, the scope of gene networks and biological mechanisms underlying suicide has yet to be defined. Previously, we reported genome-wide evidence that neurexin 1 (NRXN1), a key synapse organizing molecule, is associated with familial suicide risk. Here we present new evidence for two non-synonymous variants (rs78540316; P469S and rs199784139; H885Y) associated with increased familial risk of suicide death. We tested the impact of these variants on binding interactions with known partners and assessed functionality in a hemi-synapse formation assay. Although the formation of hemi-synapses was not altered with the P469S variant relative to wild-type, both variants increased binding to the postsynaptic binding partner, leucine-rich repeat transmembrane neuronal 2 (LRRTM2) in vitro. Our findings indicate that variants in NRXN1 and related synaptic genes warrant further study as risk factors for suicide death.

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