Sex Dimorphism · Molecular circuits of sex dimorphism in cardiometabolic traits and risk factors

Molecular circuits of sex dimorphism in cardiometabolic traits and risk factors

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 focused on understanding observational sex differences in cardiometabolic risk factors, and on the study of the genetic and molecular components that differentially impact males and females. To reach these objectives, I first performed a systematic analysis of sex and age-dependent sex differences for 70 cardiometabolic risk factors included in the SardiNIA cohort, such as blood test parameters, anthropometric measurements, blood pressure, echocardiogram and electrocardiogram measures by fitting a generalized additive model with integrated smoothness estimation. Secondly, I used sex-specific pQTL summary statistics from the UK Biobank Pharma Proteomics Project, along with sex-specific GWAS summary statistics of lipids from the Global Lipids Genetics Consortium. I combined these using two-sample Mendelian Randomization analyses and applying stringent multiple testing p-values correction and sensitivity analyses to identify proteins that are causally linked to lipids in a sex-specific or sex-differentiated manner. These results will lead to the discovery of new drug target to perform equally well in males and females and will contribute to the improvement of personalized and precision medicine in the near future.

Data: CORDIS, © European Union