University of Groningen Decoding non-coding RNAs in fatty liver disease Atanasovska, Biljana

University of Groningen

Decoding non-coding RNAs in fatty liver disease

Atanasovska, Biljana

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2019

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Atanasovska, B. (2019). Decoding non-coding RNAs in fatty liver disease. University of Groningen.

Copyright

Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the

author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

Take-down policy

If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately

and investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the

number of authors shown on this cover page is limited to 10 maximum.

Decoding non-coding RNA

s

in fatty liver disease

The research described in this thesis was conducted at the Department of Pediatrics,

Section Molecular Genetics, and the Department of Genetics, University Medical Centre

Groningen, the Netherlands. This work was mainly supported by funding from the

Systems Biology Center for Metabolism and Ageing, Groningen, the Netherlands

(SBC-EMA to C.W., M.H. and J.F.) and the Netherlands Organization for Scientific Research

(NWO-VIDI 864.13.013 to J.F.).

The printing of this dissertation was financially supported by:

The University of Groningen

The University Medical Centre Groningen

The Groningen University Institute for Drug Exploration (GUIDE)

© Biljana Atanasovska, 2019

No part of this book may be reproduced, stored in retrieval system, or transmitted in any

form or by any means without prior permission of the author or, where applicable, the

publisher holding the copyright on the published articles.

Printed by:

Proefschriftmaken.nl

Designed by:

SVDH Media | www.svdhmedia.nl

ISBN:

978-94-6380-336-6

ISBN (e-book): 978-94-6380-341-0

Decoding non-coding RNAs in fatty

liver disease

PhD thesis

to obtain the degree of PhD at the

University of Groningen

on the authority of the

Rector Magnificus prof. E. Sterken

and in accordance with

the decision by the College of Deans.

This thesis will be defended in public on

Monday 20 May 2019 at 12.45 hours

by

Biljana Atanasovska

born on 18 April 1985

in Skopje, Macedonia

Decoding non-coding RNAs in fatty

liver disease

PhD thesis

to obtain the degree of PhD at the

University of Groningen

on the authority of the

Rector Magnificus prof. E. Sterken

and in accordance with

the decision by the College of Deans.

This thesis will be defended in public on

Monday 20 May 2019 at 12.45 hours

by

Biljana Atanasovska

born on 18 April 1985

in Skopje, Macedonia

Supervisors

Prof. J. Yang-Fu

Prof. T.N. Wijmenga

Assessment Committee

Prof. A.K. Groen

Prof. A. van den Berg

Prof. J.A. Lisman

Table of Contents

Chapter 1

General introduction

9

Chapter 2

GWAS as a driver of gene discovery in cardiometabolic diseases

31

Chapter 3

A liver-specific long non-coding RNA with a role in cell viability

is elevated in human non-alcoholic steatohepatitis

53

Chapter 4

Genome-wide transcriptome analysis of livers from obese subjects

reveals lncRNAs associated with progression of fatty liver to

nonalcoholic steatohepatitis

85

Chapter 5

Functional genomics of stimulated human hepatocytes reveal a

novel long non-coding RNA involved in liver inflammation via

the NF-kB pathway

119

Chapter 6

Predicted transcribed enhancers in the liver show association with

disease, genetics and gene expression

149

Chapter 7

General discussion and future perspectives

171

Appendices

Summary

186

Samenvatting in het Nederlands

190

Acknowledgements

194

Publication list

198