Genome wide analysis of rare copy number variations in alcohol abuse or dependence
| Autor: | Ana María González, Julio Bobes, María José Páramo, Rocío Villa, Eduardo Paz, Ana María López-Crecente, Nicolás López, Raquel Calvo, Manuel Serrano, Vanessa Blanco, Ana María García, J. Rodríguez, Jesús Osorio, Xaquín Gurriarán, Carmen Rubio, Domingo Miguel, Indalecio Carrera, Emilio Fariñas, José Manuel Mesa Fernández, Manuel Arrojo, Mario Páramo, Valentín Estévez, Marta Gómez-Ramiro, Pilar A. Saiz, Julia Rodríguez-Revuelta, María Jesús Longo, Gerardo Flórez, Leonor Riera, Manuela Matalobos, Fernando L. Vázquez, Lorena de la Fuente, Rocío Herrero, Sandra Álvarez, Joaquín Pomares, Carlos Martin, Javier Costas, Jesús Gómez-Trigo, Paz García-Portilla, Julio Rodriguez-Lopez, Carlos Pino, José Portes, Ángeles Lorenzo, César Pereiro, Manuela Pérez, Francisco Díaz-Llenderozas |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine DNA Copy Number Variations Genotype Alcohol abuse Single-nucleotide polymorphism Alcohol use disorder Biology Tourette syndrome Young Adult 03 medical and health sciences 0302 clinical medicine mental disorders medicine Humans Copy-number variation Genotyping Biological Psychiatry Aged Genetics Middle Aged medicine.disease Alcoholism Psychiatry and Mental health Logistic Models 030104 developmental biology Spain Schizophrenia Autism Female 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Journal of Psychiatric Research. 103:212-218 |
| ISSN: | 0022-3956 |
| DOI: | 10.1016/j.jpsychires.2018.06.001 |
| Popis: | Genetics plays an important role in alcohol abuse/dependence. Its heritability has been estimated as 45-65%. Rare copy number variations (CNVs) have been confirmed as relevant genetic factors in other neuropsychiatric disorders, such as autism spectrum disorders, schizophrenia, epilepsy, or Tourette syndrome. In the present study, we analyzed the role of rare CNVs affecting exons of coding genes in a sample from Northwest Spain genotyped using the Illumina Infinium PsychArray Beadchip. After rigorous genotyping quality control procedure, 712 patients with alcohol abuse or dependence and 804 controls were used for CNV detection. CNV calling was performed using PennCNV and cnvPartition, and analyses were restricted to CNVs of at least 100 kb and including at least 10 single nucleotide polymorphisms. Logistic regression was used to test for the effect of CNV as well as number of genes affected by CNVs on case/control status, after adjustment for demographic and experimental covariates. We have found an excess of deletions (p = 0.008) and genes affected by deletions (p = 0.017) in cases. This effect was restricted to the 14.8% of affected genes that are intolerant to loss-of-function mutations (gene count p = 0.009). The importance of this subset of genes is emerging in other psychiatric disorders of neurodevelopmental origin, suggesting that disturbance in neurodevelopment mediated by genetic alterations may be a risk factor for alcohol use disorder. |
| Databáze: | OpenAIRE |
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