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CORDIS

Molecular circuits of sex dimorphism in cardiometabolic traits and risk factors

Project description

Unveiling the molecular impact of gender on cardiovascular disease

The sex-based difference in the presentation, severity and diagnosis of cardiovascular diseases is well documented, with oestrogen playing a protective role in women, who develop these disorders most often after menopause. Funded by the Marie Skłodowska-Curie Actions programme, the Sex Dimorphism project is interested in understanding the underlying aetiology. To achieve this, researchers will undertake sex-specific genome-wide association studies for cardiovascular diseases, type 2 diabetes, hypertension and obesity. They will then combine these with gene expression and protein changes. The key objective is to identify sex-specific causal gene networks that are responsible for the gender-biased emergence of cardiometabolic traits and modulation of risk factors.

Objective

Cardiometabolic traits and risk factors including cardiovascular diseases, type 2 diabetes, and hypertension are the leading causes of death worldwide. These conditions exhibit some degree of sex differences, including differences in incidence or prevalence, age of onset, severity, disease progression, susceptibility, response to treatment and pharmacological adverse events. Unfortunately, the reasons behind this sex dimorphism are largely unknown, hampering the realization of an effective personalized medicine.
My project will focus on understanding the genetic and molecular components that differentially impact men and women. I will first carry out sex stratified genome-wide association studies for cardiovascular diseases, type 2 diabetes, hypertension and obesity using large population biobanks to evaluate the effects of known-genetic variants within each sex and to identify novel loci that may have been previously undetected. I will then use molecular quantitative trait loci (QTLs) to identify specific gene expression changes and proteins modulated by these variants and that are likely to be involved in sex-specific development of cardiometabolic traits and modulation of risk factors. I will then validate putative causal genes using Mendelian randomization approaches.
This will lead to optimize therapeutics and find new drug target to perform equally well in males and females and will open the door to improve personalized and precision medicine in the near future.

Coordinator

CONSIGLIO NAZIONALE DELLE RICERCHE
Net EU contribution
€ 172 750,08
Address
PIAZZALE ALDO MORO 7
00185 Roma
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Research Organisations
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Total cost
No data