Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients

• Published in: Journal of psychiatric research Vol. 44; no. 14; pp. 971 - 978
• Main Authors: Saus, Ester, Brunet, Anna, Armengol, Lluís, Alonso, Pino, Crespo, José M, Fernández-Aranda, Fernando, Guitart, Miriam, Martín-Santos, Rocío, Menchón, José Manuel, Navinés, Ricard, Soria, Virginia, Torrens, Marta, Urretavizcaya, Mikel, Vallès, Vicenç, Gratacòs, Mònica, Estivill, Xavier
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-10-2010; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Anxiety; Anxiety Disorders - genetics; Anxiety-Depression; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - genetics; Catechol O-Methyltransferase - genetics; CNS (central nervous system) candidate genes; CNVs (copy number variants); copy number; Depression; Diagnostic and Statistical Manual of Mental Disorders; DNA Copy Number Variations; Eating disorders; Feeding and Eating Disorders - genetics; Female; GABA Plasma Membrane Transport Proteins - genetics; Genes; Genetic Predisposition to Disease; Genome, Human; Genomes; genomics; Humans; Male; Medical sciences; Mental disorders; Mental Disorders - diagnosis; Mental Disorders - genetics; Mentally ill people; Middle Aged; Miscellaneous; MLPA; Mood; Mood Disorders - genetics; Nerve Growth Factors - genetics; Neural Pathways - metabolism; Neuropeptides - genetics; Polymerase Chain Reaction; Psychiatric disorders; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rare variants; Receptors, Metabotropic Glutamate - genetics; Receptors, Somatostatin - genetics; Risk factors; S100 beta protein; S100 Calcium Binding Protein beta Subunit; S100 Proteins - genetics; Schizophrenia; Schizophrenia - genetics; Statistical analysis; Variants; CNVs (copy number variants); CNS (central nervous system) candidate genes; MLPA; Psychiatric disorders; Rare variants; Human; Pathophysiology; Copy number; Genetic variant; Central nervous system; Genetic determinism; Encephalon; CNS (central nervous system); candidate genes; Mental disorder; Genetics; Candidate gene
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2010.03.007

Abstract Background Copy number variations (CNV) have become an important source of human genome variability noteworthy to consider when studying genetic susceptibility to complex diseases. As recent studies have found evidences for the potential involvement of CNVs in psychiatric disorders, we have studied the dosage effect of structural genome variants as a possible susceptibility factor for different psychiatric disorders in a candidate gene approach. Methods After selection of 68 psychiatric disorders’ candidate genes overlapping with CNVs, MLPA assays were designed to determine changes in copy number of these genes. The studied sample consisted of 724 patients with psychiatric disorders (accounting for anxiety disorders, mood disorders, eating disorders and schizophrenia) and 341 control individuals. Results CNVs were detected in 30 out of the 68 genes screened, indicating that a considerable proportion of neuronal pathways genes contain CNVs. When testing the overall burden of rare structural genomic variants in the different psychiatric disorders compared to control individuals, there was no statistically significant difference in the total amount of gains and losses. However, 14 out of the 30 changes were only found in psychiatric disorder patients but not in control individuals. These genes include GRM7 , previously associated to major depression disorder and bipolar disorder, SLC6A13 , in anxiety disorders, and S100B , SSTR5 and COMT in schizophrenia. Conclusions Although we have not been able to found a clear association between the studied CNVs and psychiatric disorders, the rare variants found only within the patients could account for a step further towards understanding the pathophysiology of psychiatric disorders.