Project Description
SEX DIMORPHISM
Molecular circuits of sex dimorphism in cardiomethabolic traits and risk factors
Sex Dimorphism is the project 101066678 (https://cordis.europa.eu/project/id/101066678)
developed by Daniela Zanetti under the supervision of Serena Sanna at the Institute of Genetic and Biomedical Research (IRGB) of the National Research Council (CNR) of Cagliari.
This project aims to understand the genetic and molecular components that differentially impact men and women in cardiometabolic traits and risk factors. These conditions exhibit some degree of sex differences, including differences in incidence or prevalence, age of onset, severity, disease progression, and response to treatment and pharmacological adverse events. Unfortunately, the reasons behind this sex dimorphism are largely unknown.
The mechanistic findings of the project are going to be highly relevant, especially for clinical and pharmaceutical sectors. These insights will accelerate the development of new sex-tailored prevention strategies, through potential sex specific druggable targets that may be pivotal for personalized and precision medicine.
Funding sources:
The project is funded by the MSCA Postdoctoral Fellowships 2021.
Research Team:
The project is led by Daniela Zanetti, researcher at the IRGB-CNR, and supervised by Serena Sanna, head of research at the IRGB-CNR.
Collaborators:
Several collaborators from the University of Stanford (California) and from the University of Groningen (NL) will be involved in the project.
Relevant links:
Results:
The results of the Sex Dimorphism project are part of a manuscript titled “Exploring sex-specific causal links between thousands of proteins and lipid metabolism using the UK Biobank Pharma proteomics data” available on MedrXiv at this link https://medrxiv.org/cgi/content/short/2025.09.16.25335948v1
This manuscript highlights several proteins with sex-specific and sex-differentiated causal impact on lipid levels. Several of these proteins were previously shown to be involved in inflammation and cardiometabolic disease, such as Apolipoprotein(a) and lipoprotein lipase. These results provide insight into potential genetic drivers of sex dimorphism in lipid metabolism. Such knowledge may in turn improve the predictive use of sex-specific pQTLs and point to new therapeutic gender specific strategies to prevent cardiovascular diseases. Furthermore, my approach provides a proof-of-concept of the utility of sex-stratifed pQTLs and GWAS. Thus, my work, encourages all future GWAS of any complex trait and disease to follow this strategy as route to derive relevant insights into potential genetic drivers of sex dimorphism not only in lipid metabolism.