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Distinguishing genetic overlap and causal relationship among attention deficit-hyperactivity disorder and substance use disorders

Project description

Insight into the association between attention-deficit and substance abuse disorders

Emerging evidence indicates that attention-deficit/hyperactivity disorder (ADHD) is highly prevalent among individuals that suffer from substance use disorders (SUDs). The EU-funded ATTENTIVE project aims to shed light on the biological basis and the mechanism underlying the pathogenic association between ADHD and SUDs. Researchers will look for shared risk alleles in large genome-wide association data sets and identify transcriptomic and epigenomic changes. They will use induced pluripotent stem cells as a model to validate their findings and pave the way for preventive strategies and therapeutic approaches against substance abuse in high-risk individuals.

Objective

The ATTENTIVE project will deliver a comprehensive training-through-research to a talented postdoctoral fellow in two leading multi-disciplinary research groups. I will bring clinical, molecular biology and genetic skills and I will receive extensive training in state-of-the-art genomic data science and cell biology, creating a two-way transfer. The proposed work will expand my experience, research competencies and professional networks, leading to the possibility to become an independent researcher. The research part of the proposal is focused on understanding the biological basis of the comorbidity observed between Attention Deficit-Hyperactivity Disorder (ADHD) and Substance Use Disorders (SUDs), as it is unclear which the underlying mechanisms are. Using large-scale genome-wide association study (GWAS) datasets , we will test whether this epidemiological and genetic correlation is due to shared risk alleles acting independently on both disorders or to causal effects between the disorders. We will combine different analytical methods, leveraging genome-wide data and brain-specific information related to additional omics domains. We will derive information regarding transcriptomic and epigenomic changes in brain tissues and cells. GWASs can identify a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Therefore, we will validate the results through induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. The iPSCs carrying the variants significant from the GWAS will be differentiated to neural cells and neural mRNA will be analyzed by RNA-Seq. The expected results will provide novel information regarding the molecular mechanisms at the basis of this pathogenic association, also providing insights that could contribute to develop preventive strategies and therapeutic approaches to address substance abuse and alcohol dependence in subjects with ADHD, a high-risk category.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

UNIVERSITAT DE BARCELONA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 263 732,16
Address
GRAN VIA DE LES CORTS CATALANES 585
08007 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 263 732,16

Partners (1)

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