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

Ester Saus, Anna Brunet, Lluís Armengol, Pino Alonso, José M. Crespo, Fernando Fernández-Aranda, Miriam Guitart, Rocío Martín-Santos, José Manuel Menchón, Ricard Navinés, Virginia Soria, Marta Torrens, Mikel Urretavizcaya, Vicenç Vallès, Mònica Gratacòs, Xavier P. Estivill

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)971-978
Number of pages8
JournalJournal of Psychiatric Research
Volume44
Issue number14
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Fingerprint

Psychiatry
Genes
Genomic Structural Variation
Anxiety Disorders
Schizophrenia
Overlapping Genes
Gene Dosage
Human Genome
Genetic Predisposition to Disease
Mood Disorders
Bipolar Disorder
Depression

Keywords

  • CNS (central nervous system) candidate genes
  • CNVs (copy number variants)
  • MLPA
  • Psychiatric disorders
  • Rare variants

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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

In: Journal of Psychiatric Research, Vol. 44, No. 14, 10.2010, p. 971-978.

Research output: Contribution to journalArticle

Saus, E, Brunet, A, Armengol, L, Alonso, P, Crespo, JM, Fernández-Aranda, F, Guitart, M, Martín-Santos, R, Menchón, JM, Navinés, R, Soria, V, Torrens, M, Urretavizcaya, M, Vallès, V, Gratacòs, M & Estivill, XP 2010, 'Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients', Journal of Psychiatric Research, vol. 44, no. 14, pp. 971-978. https://doi.org/10.1016/j.jpsychires.2010.03.007
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 P. / Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients. In: Journal of Psychiatric Research. 2010 ; Vol. 44, No. 14. pp. 971-978.
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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.",
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AU - Brunet, Anna

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AU - Crespo, José M.

AU - Fernández-Aranda, Fernando

AU - Guitart, Miriam

AU - Martín-Santos, Rocío

AU - Menchón, José Manuel

AU - Navinés, Ricard

AU - Soria, Virginia

AU - Torrens, Marta

AU - Urretavizcaya, Mikel

AU - Vallès, Vicenç

AU - Gratacòs, Mònica

AU - Estivill, Xavier P.

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N2 - 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.

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