NRXN1 is associated with enlargement of the temporal horns of the lateral ventricles in psychosis.
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Alliey-Rodriguez Ney, Grey Tamar A, Shafee Rebecca, Asif Huma, Lutz Olivia, Bolo Nicolas R, Padmanabhan Jaya, Tandon Neeraj, Klinger Madeline, Reis Katherine, Spring Jonathan, Coppes Lucas, Zeng Victor, Hegde Rachal R, Hoang Dung T, Bannai Deepthi, Nawaz Uzma, Henson Philip, Liu Siyuan, Gage Diane, McCarroll Steven, Bishop Jeffrey R, Hill Scot, Reilly James L, Lencer Rebekka, Clementz Brett A, Buckley Peter, Glahn David C, Meda Shashwath A, Narayanan Balaji, Pearlson Godfrey, Keshavan Matcheri S, Ivleva Elena I, Tamminga Carol, Sweeney John A, Curtis David, Badner Judith A, Keedy Sarah, Rapoport Judith, Liu Chunyu, Gershon Elliot S
Аннотация
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.