Genetic and methodological aspects of statin-induced lipid response

Smit, R.A.J. (2019)

Doctoral Thesis

This thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis on statin-induced HDL-C response by the Genomic Investigation of consortium, which identified CETP as a loci of interest, and two-sample Mendelian randomization studies utilizing summary level data from the GIST and other GWAS consortia on fasted blood lipids and type 2 diabetes. We additionally examine the issue of survival bias in Mendelian randomization studies. Finally, we show that intra-individual lipid variability associates with worse neurocognitive outcomes in older individuals at high risk for vascular disease, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest.

• Mendelian randomization
• Lipids
• Statins
• GWAS
• Pharmacogenetics
• Cardiovascular disease
• Genetics

• All authors: Smit, R.A.J.
• Supervisor: Jukema, J.W.; Cessie, S. le
• Co-supervisor: Trompet, S.
• Committee: Slagboom, P.E.; Stroes, E.S.G.; Swanson, S.A.; Mook-Kanamori, D.O.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University of Medical Center [LUMC], Leiden University
• Date: 2019-04-18
• ISBN (print): 9789463753029
• Sponsorship: Dutch Heart Foundation