Leiden University Scholarly Publications

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Luijk, R. (2019)

From correlation to causation: Data-driven exploration of transcriptional regulation using population genomics

Doctoral Thesis
In this thesis, we aimed to better understand how genetic variation affect the processes underlying health and disease, as trait-associated genetic variants are often located in non-coding regions. This hampers their interpretability, and has prompted the exploration of their effects on transcriptional regulation, a process that is crucial in the development of common and complex diseases. To do this, we have used a variety of omics data in a large collection of individuals from the general population. Using these data, we have investigated the local and distal effects of genetic variants on other molecular phenotypes, such as gene expression levels and DNA methylation levels of CpG sites, and the underlying mechanisms. This has resulted in a framework enabling the exploration of causal hypotheses about transcriptional regulation using genetics as a causal anchor. The approaches used in this thesis have yielded insight into transcriptional (dys)regulation...Show moreIn this thesis, we aimed to better understand how genetic variation affect the processes underlying health and disease, as trait-associated genetic variants are often located in non-coding regions. This hampers their interpretability, and has prompted the exploration of their effects on transcriptional regulation, a process that is crucial in the development of common and complex diseases. To do this, we have used a variety of omics data in a large collection of individuals from the general population. Using these data, we have investigated the local and distal effects of genetic variants on other molecular phenotypes, such as gene expression levels and DNA methylation levels of CpG sites, and the underlying mechanisms. This has resulted in a framework enabling the exploration of causal hypotheses about transcriptional regulation using genetics as a causal anchor. The approaches used in this thesis have yielded insight into transcriptional (dys)regulation and several underlying mechanisms. This will be helpful in better understanding how transcriptional regulation contributes to complex phenotypes related to health and disease, such as common diseases. Show less
Epigenomics
Genomics
Causality
Transcriptional regulation
All authors
Luijk, R.
Supervisor
Slagboom, P.
Co-supervisor
Heijmans, B.T.; Zwet, E.W.van
Committee
Boomsma, D.I.; Cannegieter, S.C.; Goeman, J.J.; Gribnau, J.H.
Qualification
Doctor (dr.)
Awarding Institution
Leiden University of Medical Center [LUMC], Leiden University
Date
2019-10-16
ISBN (print)
9789463805360