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 Gage, Steven 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

Journal: Translational psychiatry 2020;9(1):230

PMID: 31530798

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.

Address: University of Chicago, Department of Psychiatry and Behavioral Neurosciences, Chicago, USA. [email protected].; Massachusetts Institute of Technology, Cambridge, USA.; Harvard Medical School, Department of Genetics, Boston, USA.; Stanley Center, Broad Institute of MIT and Harvard, Cambridge, USA.; University of Chicago, Department of Psychiatry and Behavioral Neurosciences, Chicago, USA.; Harvard Medical School, Department of Psychiatry, Boston, USA.; University of Chicago Laboratory for Advanced Computing, Chicago, USA.; Harvard University, Cambridge, USA.; Boston University, Boston, USA.; Child Psychiatry Branch, National Institutes of Mental Health, National Institutes of Health, Bethesda, MD, USA.; Broad Institute of MIT and Harvard, Cambridge, USA.; University of Minnesota, Department of Experimental and Clinical Pharmacology and Department of Psychiatry, Minneapolis, USA.; Rosalind Franklin University, North Chicago, USA.; Northwestern University, Evanston, USA.; University of Muenster, Munster, Germany.; Department of Psychology, University of Georgia, Athens, Georgia.; Virginia Commonwealth University, Richmond, USA.; Yale University Departments of Psychiatry & Neuroscience, New Haven, USA.; University of Texas Southwestern Medical Center, Department of Psychiatry, Dallas, USA.; University College London and Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, London, UK.; Rush University Medical Center, Chicago, USA.; SUNY Upstate Medical University, Binghamton, USA.; University of Chicago, Department of Psychiatry and Behavioral Neurosciences, Chicago, USA. [email protected].; University of Chicago, Department of Human Genetics, Chicago, USA. [email protected].
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