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 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.