Genetic and metabolomic approaches for coronary heart disease risk prediction

Author(s):
Vaarhorst, A.A.M.
Published
2014
Publication type
Doctoral Thesis

Abstract

The prediction of coronary heart disease (CHD) risk is currently based on traditional risk factors (TRFs) like age, sex, lipid levels, blood pressure. Here we investigated, using the CAREMA cohort, whether this prediction can potentially be improved by applying a metabolomics approach and by including information on single nucleotide polymorphisms (SNPs) previously reported to be relevant for cardiovascular disease risk. Based on the results described in this thesis it can be concluded that a metabolomics profile generated by 1H-NMR spectroscopy when combined with age and sex could mark individuals at high risk for cardiovascular disease. The performance of that method was comparable to a score based on TRFs. It was also found that a weighted genetic risk score based 29 SNPs associated with CHD marginally improved CHD risk prediction. In the Leiden Longevity Study it was examined if comprehensive lipid profiles could mark metabolic health in middle-aged individuals. We found that male metabolic health was characterized by LDL particle size and female metabolic health was characterized by triglyceride levels. Finally it was observed that an increased delta-5 desaturase activity was protective against CHD. This effect was mainly observed in AA carriers of a SNP located in FADS1

LASSO-regressionCase-cohortGenetic-risk-scoreGWASLipidsLongevityDesaturasesCox-regressionMetabolites1H-NMR
Defense date
2014-05-13
Language
English
Supervisor(s)
Slagboom, P.
Advisor(s)
Heijmans, B.T.
Qualification
Ph.D.
Degree granting institution
Faculty of Medicine (LUMC), Leiden University, Leiden
hdl
1887/25760
ISBN(s)
9789088918698

Funding

Sponsorship
The research described in this thesis was supported by a grant of the Dutch Heart Foundation (DHF-2006B195) and by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. Financial support for the printing of this thesis was provided by the Netherlands Consortium for Healthy Ageing (GI 050060810). Nederlandse Hartstichting Netherlands Consortium for Healthy Ageing (GI 050060810)