Cover Page
The handle
http://hdl.handle.net/1887/136917
holds various files of this Leiden University
dissertation.
Author: Bos, M.M.
GENETIC AND ENVIRONMENTAL DETERMINANTS
OF CARDIOMETABOLIC HEALTH
Genetic and environmental determinants of cardiometabolic health © 2020, M.M. Bos
Cover design and layout: © evelienjagtman.com Printing: Optima Grafische Communicatie ISBN: 978-94-6361-461-0
All rights reserved. No part of this thesis may be transformed, reproduced or transmitted in any form and by any means without prior permission of the author.
GENETIC AND ENVIRONMENTAL DETERMINANTS
OF CARDIOMETABOLIC HEALTH
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,
door besluit van het College voor Promoties, te verdedigen op donderdag 1 oktober 2020,
klokke 11.15 uur
door Maxime M Bos geboren te Purmerend
Promotor
Prof. dr. G.J. Blauw Co-promotores Dr. ir. D. van Heemst Dr. R. Noordam
Leden promotiecommissie Prof. dr. P.C.N. Rensen
Prof. P. Parini (Karolinska Institutet, Stockholm, Sweden)
Dit proefschrift draag ik op aan mijn lieve vader,
KANSEN KRIJG JE NIET, DIE MOET JE CREËREN
TABLE OF CONTENTS
Chapter 1 General introduction and thesis outline 9
Part I Metabolomics and glucose metabolism
Chapter 2 Metabolomics analyses in non-diabetic middle-aged individuals reveal metabolites impacting early glucose disturbances and insulin sensitivity
23
Part II Sleep
Chapter 3.1 Associations between sleep duration and quality with serum and hepatic lipids: the Netherlands Epidemiology of Obesity Study.
49
Chapter 3.2 The association between habitual sleep duration and sleep quality with glycemic traits: assessment by cross-sectional and Mendelian Randomization analyses
67
Chapter 3.3 Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.
89
Part III APOE
Chapter 4.1 The ApoE ε4 Isoform: Can the Risk of Diseases be Reduced by Environmental Factors?
121 Chapter 4.2 Apolipoprotein E genotype, lifestyle and coronary artery
disease: gene-environment interaction analyses in the UK Biobank population
145
Part IV Thyroid status and diabetes
Chapter 5.1 Thyroid Signaling, Insulin Resistance, and 2 Diabetes Mellitus: A Mendelian Randomization Study
165 Chapter 5.2 Genetically-determined higher TSH is associated with
lower diabetes mellitus risk in individuals with low BMI: results from the UK Biobank
187
Part V Discussion, summaries and non-scientific part
Chapter 6 General discussion and future perspectives 205
Chapter 7.1 English summary 217
Chapter 7.2 Nederlandse samenvatting 223
Chapter 7.3 Curriculum Vitae 229
