Genetics and life course epidemiology of cardiometabolic disease: towards personalized medicine

Ibi, D. (2023)

Doctoral Thesis

In the first part of this thesis we focus on the genetic determinants of lipid metabolism as atherogenic dyslipidemia is major component of cardiometabolic disease and consequently of CVD. In the second part of the thesis, we study the age-related changes of cardiometabolic risk factors over the life course across four generations. In this thesis, we aimed to gain new insights into the underlying pathophysiology of cardiometabolic disease and the long-term and cumulative exposure of its risk factors over the life course, thereby facilitating the search for preventive and curative strategies of cardiometabolic disease. In the first part of this thesis, we focused on the genetic determinants of lipid metabolism during both fasting and postprandial states. In the second part, we studied the age-related changes of cardiometabolic risk factors, in particular of body weight, overweight and obesity, over the life course across four generations. An important finding of the thesis is that obesity has worsened in the younger generations, reaching almost double the prevalence of older generations. However, after midlife the levels of obesity levelled off, which could be a reason why the adverse shift in obesity was not associated with unfavourable changes in cardiometabolic risk factors. We also found out that some genes effect body weight differently at different ages, which suggests that gene-environment interactions play an important role in body weight and consequently in obesity.

• Cardiovascular disease
• Obesity
• Lipid Metabolism
• Genetics
• Environmental factors
• Mendelian Randomization
• Body mass index (BMI)
• Life course epidemiology
• Single nucleotide polymorphism (SNP)
• Personalized Medicine

• All authors: Ibi, D.
• Supervisor: Willems van Dijk, J.A.P.; Verschuren, W.M.M.
• Co-supervisor: Dollé, M.E.T.
• Committee: Heijmans, B.T.; Rensen, P.C.N.; Houtkooper, R.H.L.; Meurs, J.B.J. van
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2023-02-21
• ISBN (print): 9789463618106