Midway evaluation in Statistics - Sölvi Rögnvaldsson

Title of thesis: Uncovering genetic interactions and their role in human traits and diseases

Student: Sölvi Rögnvaldsson

Advisor: Dr. Daníel Fannar Guðbjartsson, Guest professor at the Faculty of Physical Sciences and Chief Scientist at deCODE

Co Advisor: Dr. Sædís Sævarsdóttir, Professor and Dean of the Faculty of Medicine, University of Iceland

Doctoral Committee:
Dr. Rósa B. Þórólfsdóttir, Scientist at deCODE
Dr. Birgir Hrafnkelsson, Professor at the Faculty of Physical Sciences, University of Iceland
Dr. Matti J Pirinen, Professor of Statistics at the Department of Mathematics and Statistics & Department of Public Health University of Helsinki, Finland.

Faculty supervisor: Dr. Sigrún Helga Lund, Professor at the Faculty of Physical Sciences, University of Iceland

Abstract

Genome-wide association studies (GWASs) have identified thousands of genetic loci linked with human phenotypes, yet estimates of the variance attributed to genetics (heritability) remain lower than those from twin studies. This discrepancy could in part be because GWAS only capture additive effects, overlooking gene-gene (epistasis) and gene-environment interactions. Such interactions are not only relevant in the context of the heritability gap, but can also give insight into the dynamics of biological processes as well as help explaining individual responses to interventions such as medications or supplementations. However, detecting them has been challenging due to limited power and combinatorial complexity of testing all gene-gene interaction pairs. The aim of this PhD project is to leverage the extensive phenotypic and genotypic resource at Amgen deCODE genetics to develop methods for identifying and understanding genetic interactions underlying human phenotypes at scale. The presentation will focus on the first two papers of the PhD, one looking into temporal changes of the genetic effect on childhood BMI across the 20th century in Iceland, while the second one describes both gene-gene and gene-environment interaction effects on thyroid function and diseases.