Ingrid A C Romme1, Marcel A de Reus1, Roel A Ophoff2, René S Kahn1, Martijn P van den Heuvel3. 1. Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. 2. Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Center for Neurobehavioral Genetics and Department of Human Genetics , University of California Los Angeles, Los Angeles, California. 3. Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: M.P.vandenheuvel@umcutrecht.nl.
Abstract
BACKGROUND: Genome-wide association studies have identified several common risk loci for schizophrenia (SCZ). In parallel, neuroimaging studies have shown consistent findings of widespread white matter disconnectivity in patients with SCZ. METHODS: We examined the role of genes in brain connectivity in patients with SCZ by combining transcriptional profiles of 43 SCZ risk genes identified by the recent genome-wide association study of the Schizophrenia Working Group of the Psychiatric Genomics Consortium with data on macroscale connectivity reductions in patients with SCZ. Expression profiles of 43 Psychiatric Genomics Consortium SCZ risk genes were extracted from the Allen Human Brain Atlas, and their average profile across the cortex was correlated to the pattern of cortical disconnectivity as derived from diffusion-weighted magnetic resonance imaging data of patients with SCZ (n = 48) and matched healthy controls (n = 43). RESULTS: The expression profile of SCZ risk genes across cortical regions was significantly correlated with the regional macroscale disconnectivity (r = .588; p = .017). In addition, effects were found to be potentially specific to SCZ, with transcriptional profiles not related to cortical disconnectivity in patients with bipolar I disorder (diffusion-weighted magnetic resonance imaging data; 216 patients, 144 controls). Further examination of correlations across all 20,737 genes present in the Allen Human Brain Atlas showed the set of top 100 strongest correlating genes to display significant enrichment for the disorder, potentially identifying new genes involved in the pathophysiology of SCZ. CONCLUSIONS: Our results suggest that under disease conditions, cortical areas with pronounced expression of risk genes implicated in SCZ form central areas for white matter disconnectivity.
BACKGROUND: Genome-wide association studies have identified several common risk loci for schizophrenia (SCZ). In parallel, neuroimaging studies have shown consistent findings of widespread white matter disconnectivity in patients with SCZ. METHODS: We examined the role of genes in brain connectivity in patients with SCZ by combining transcriptional profiles of 43 SCZ risk genes identified by the recent genome-wide association study of the Schizophrenia Working Group of the Psychiatric Genomics Consortium with data on macroscale connectivity reductions in patients with SCZ. Expression profiles of 43 Psychiatric Genomics Consortium SCZ risk genes were extracted from the Allen Human Brain Atlas, and their average profile across the cortex was correlated to the pattern of cortical disconnectivity as derived from diffusion-weighted magnetic resonance imaging data of patients with SCZ (n = 48) and matched healthy controls (n = 43). RESULTS: The expression profile of SCZ risk genes across cortical regions was significantly correlated with the regional macroscale disconnectivity (r = .588; p = .017). In addition, effects were found to be potentially specific to SCZ, with transcriptional profiles not related to cortical disconnectivity in patients with bipolar I disorder (diffusion-weighted magnetic resonance imaging data; 216 patients, 144 controls). Further examination of correlations across all 20,737 genes present in the Allen Human Brain Atlas showed the set of top 100 strongest correlating genes to display significant enrichment for the disorder, potentially identifying new genes involved in the pathophysiology of SCZ. CONCLUSIONS: Our results suggest that under disease conditions, cortical areas with pronounced expression of risk genes implicated in SCZ form central areas for white matter disconnectivity.
Authors: Marie Forest; Yasser Iturria-Medina; Jennifer S Goldman; Claudia L Kleinman; Amanda Lovato; Kathleen Oros Klein; Alan Evans; Antonio Ciampi; Aurélie Labbe; Celia M T Greenwood Journal: Hum Brain Mapp Date: 2017-03-21 Impact factor: 5.038
Authors: Lara M Wierenga; Martijn P van den Heuvel; Bob Oranje; Jay N Giedd; Sarah Durston; Jiska S Peper; Timothy T Brown; Eveline A Crone Journal: Hum Brain Mapp Date: 2017-09-28 Impact factor: 5.038