Objective
Schizophrenia (SZ) is a debilitating disorder affecting 1% of the population and shows a strong genetic component. Onset of SZ is usually before age 40, but 1.2% have onset after 40. These individuals show marked differences from earlier onset, including more female cases, improved cognition, and more paranoid symptoms. The burden of late-onset SZ (LOS) is likely to grow due to the ageing population in Europe. However, little research has been conducted on LOS and the genomics of LOS have not been examined.
Recent technological breakthroughs have allowed the interrogation of the genome to uncover the genetic underpinnings of SZ, and genome-wide association studies (GWAS) have been successful at finding replicated associated markers. To date, studies have not examined genetic differences between LOS and earlier onset cases. The proposed study will be the largest to examine clinical and genetic correlates of LOS vs normal onset (NOS; 18-39 yrs) and vs early onset (EOS; <18 yrs), with 400 LOS and 25,000 N/EOS.
Utilising WTCCC2 GWAS data (50 LOS), the minor allele of a single nucleotide polymorphism (SNP) in the gene PREX2 was GWAS-significantly more frequent in LOS vs NOS cases and this association was replicated in an independent GWAS (79 LOS). In both GWAS, the minor allele was most frequent in LOS (10-13%), intermediate in NOS (2-4%) and lowest in EOS (1-2%), suggesting a protective effect against earlier development of SZ. In controls, the frequency of the minor allele was 4-6%, indicating it was not conferring LOS-specific risk. PREX2 is part of the RAC1 pathway containing several SZ candidate genes and GWAS support association of PREX2 with working memory and processing speed. A knockout mouse model has shown SZ-related phenotypes.
Identification of genetic factors protective against developing SZ may help to develop drug targets to prevent onset. If successful, funding will help me integrate fully into TCD by providing me with the framework for a major grant.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics nucleotides
- medical and health sciences clinical medicine psychiatry schizophrenia
- natural sciences biological sciences genetics genomes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
D02 CX56 Dublin
Ireland
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