A genomic and epigenomic approach to the association between tobacco and schizophrenia (Q3139725)

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Project Q3139725 in Spain
Language Label Description Also known as
English
A genomic and epigenomic approach to the association between tobacco and schizophrenia
Project Q3139725 in Spain

    Statements

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    42,000.0 Euro
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    52,500.0 Euro
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    80.0 percent
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    1 January 2018
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    31 March 2021
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    FUNDACION INSTITUTO DE INVESTIGACION SANITARIA DE SANTIAGO DE COMPOSTELA
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    42°52'49.51"N, 8°32'45.10"W
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    15078
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    Las personas con esquizofrenia tienen una esperanza de vida aproximadamente 15 años menor que la población general, debido principalmente a hábitos de vida poco saludables, como el tabaquismo. Existe una clara asociación entre tabaco y esquizofrenia. Varias hipótesis no excluyentes explicarían esta asociación: la de la automedicación, la de la susceptibilidad compartida o la del tabaco como factor de riesgo. La principal finalidad del presente proyecto es comprobar si el tabaco es un factor de riesgo a esquizofrenia, mediante herramientas genómicas. Como objetivo adicional, se pretende contrastar la existencia de subgrupos de pacientes con características moleculares específicas asociadas al tabaco como mecanismo etiopatogénico (estratificación etiológica). Para ello, se cuenta con datos de genotipación (Illumina PsychArray) para 1838 pacientes y 2303 controles correspondientes a colecciones del CIBERSAM y de Santiago de Compostela. Inicialmente, se estratificará la muestra en función del hábito tabáquico mediante información ya existente o mediante ensayo de metilación de cg05575921 (empleando EpiTYPER, Agena Bioscience). A continuación se estimará la varianza explicada por riesgos poligénicos a partir de receptores colinérgicos nicotínicos asociados a dependencia a nicotina y esquizofrenia (datos del Psychiatric Genomics Consortium) en nuestra muestra, estratificada por hábito tabáquico. También se estimarán los riesgos poligénicos a ser fumador y a edad de inicio (datos del Tobacco and Genetics Consortium) para comparar fumadores esquizofrénicos frente a fumadores control. Por último, se analizará la posible existencia de un subgrupo de pacientes esquizofrénicos caracterizados por consumo de tabaco como factor causal mediante análisis de conjunto de genes en la comparación entre pacientes fumadores y no fumadores, así como mediante la estima de riesgos poligénicos a partir de eQTLs de genes expresados diferencialmente en cerebro por exposición al tabaco. (Spanish)
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    People with schizophrenia have a life expectancy approximately 15 years lower than the general population, mainly due to unhealthy lifestyles, such as smoking. There is a clear association between tobacco and schizophrenia. Several non-exclusive hypotheses would explain this association: self-medication, shared susceptibility or tobacco as a risk factor. The main purpose of this project is to check whether tobacco is a risk factor for schizophrenia, using genomic tools. As an additional objective, it is intended to contrast the existence of subgroups of patients with specific molecular characteristics associated with tobacco as an etiopathogenic mechanism (etiological stratification). To do this, we have genotyping data (Illumina PsychArray) for 1838 patients and 2303 controls corresponding to collections of CIBERSAM and Santiago de Compostela. Initially, the sample will be stratified according to tobacco habit using existing information or by cg05575921 methylation test (using EpiTYPER, Agena Bioscience). The variance explained by polygenic risks from nicotinic cholinergic receptors associated with nicotine dependence and schizophrenia (data from Psychiatric Genomics Consortium) in our sample, stratified by smoking habit, will be estimated below. Polygenic risks to smoking and early age (data from Tobacco and Genetics Consortium) will also be estimated to compare schizophrenic smokers to control smokers. Finally, the possible existence of a subgroup of schizophrenic patients characterised by tobacco use as a causal factor will be analysed through gene pool analysis in the comparison between smokers and non-smokers, as well as by estimating polygenic risks from gene eQTLs expressed differentially in the brain due to tobacco exposure. (English)
    12 October 2021
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    Santiago de Compostela
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    Identifiers

    PI17_01424
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