NRXN1 is associated with enlargement of the temporal horns of the lateral ventricles in psychosis

Ney Alliey-Rodriguez*, Tamar A. Grey, Rebecca Shafee, Huma Asif, Olivia Lutz, Nicolas R. Bolo, Jaya Padmanabhan, Neeraj Tandon, Madeline Klinger, Katherine Reis, Jonathan Spring, Lucas Coppes, Victor Zeng, Rachal R. Hegde, Dung T. Hoang, Deepthi Bannai, Uzma Nawaz, Philip Henson, Siyuan Liu, Diane GageSteven McCarroll, Jeffrey R. Bishop, Scot Hill, James L. Reilly, Rebekka Lencer, Brett A. Clementz, Peter Buckley, David C. Glahn, Shashwath A. Meda, Balaji Narayanan, Godfrey Pearlson, Matcheri S. Keshavan, Elena I. Ivleva, Carol Tamminga, John A. Sweeney, David Curtis, Judith A. Badner, Sarah Keedy, Judith Rapoport, Chunyu Liu, Elliot S. Gershon

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877, P = 6.76E–10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E–8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis.

Original languageEnglish (US)
Article number230
JournalTranslational psychiatry
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Alliey-Rodriguez, N., Grey, T. A., Shafee, R., Asif, H., Lutz, O., Bolo, N. R., Padmanabhan, J., Tandon, N., Klinger, M., Reis, K., Spring, J., Coppes, L., Zeng, V., Hegde, R. R., Hoang, D. T., Bannai, D., Nawaz, U., Henson, P., Liu, S., ... Gershon, E. S. (2019). NRXN1 is associated with enlargement of the temporal horns of the lateral ventricles in psychosis. Translational psychiatry, 9(1), [230]. https://doi.org/10.1038/s41398-019-0564-9