Amanda B Zheutlin1, Rachael W Viehman2, Rebecca Fortgang1, Jacqueline Borg3, Desmond J Smith4, Jaana Suvisaari5, Sebastian Therman5, Christina M Hultman6, Tyrone D Cannon1. 1. Department of Psychology, Yale University. 2. Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles. 3. Department of Clinical Neuroscience, Karolinska Institutet. 4. Department of Molecular and Medical Pharmacology, University of California Los Angeles. 5. National Institute for Health and Welfare. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
Abstract
OBJECTIVE: We performed a whole-genome expression study to clarify the nature of the biological processes mediating between inherited genetic variations and cognitive dysfunction in schizophrenia. METHOD: Gene expression was assayed from peripheral blood mononuclear cells using Illumina Human WG6 v3.0 chips in twins discordant for schizophrenia or bipolar disorder and control twins. After quality control, expression levels of 18,559 genes were screened for association with the California Verbal Learning Test (CVLT) performance, and any memory-related probes were then evaluated for variation by diagnostic status in the discovery sample (N = 190), and in an independent replication sample (N = 73). Heritability of gene expression using the twin design was also assessed. RESULTS: After Bonferroni correction (p < 2.69 × 10-6), CVLT performance was significantly related to expression levels for 76 genes, 43 of which were differentially expressed in schizophrenia patients, with comparable effect sizes in the same direction in the replication sample. For 41 of these 43 transcripts, expression levels were heritable. Nearly all identified genes contain common or de novo mutations associated with schizophrenia in prior studies. CONCLUSION: Genes increasing risk for schizophrenia appear to do so in part via effects on signaling cascades influencing memory. The genes implicated in these processes are enriched for those related to RNA processing and DNA replication and include genes influencing G-protein coupled signal transduction, cytokine signaling, and oligodendrocyte function. (c) 2015 APA, all rights reserved).
OBJECTIVE: We performed a whole-genome expression study to clarify the nature of the biological processes mediating between inherited genetic variations and cognitive dysfunction in schizophrenia. METHOD: Gene expression was assayed from peripheral blood mononuclear cells using Illumina Human WG6 v3.0 chips in twins discordant for schizophrenia or bipolar disorder and control twins. After quality control, expression levels of 18,559 genes were screened for association with the California Verbal Learning Test (CVLT) performance, and any memory-related probes were then evaluated for variation by diagnostic status in the discovery sample (N = 190), and in an independent replication sample (N = 73). Heritability of gene expression using the twin design was also assessed. RESULTS: After Bonferroni correction (p < 2.69 × 10-6), CVLT performance was significantly related to expression levels for 76 genes, 43 of which were differentially expressed in schizophreniapatients, with comparable effect sizes in the same direction in the replication sample. For 41 of these 43 transcripts, expression levels were heritable. Nearly all identified genes contain common or de novo mutations associated with schizophrenia in prior studies. CONCLUSION: Genes increasing risk for schizophrenia appear to do so in part via effects on signaling cascades influencing memory. The genes implicated in these processes are enriched for those related to RNA processing and DNA replication and include genes influencing G-protein coupled signal transduction, cytokine signaling, and oligodendrocyte function. (c) 2015 APA, all rights reserved).
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