Ingrid Kockum's research group

Genetic Epidemiology of Multiple Sclerosis

Our aim is to identify genetic risk factors for multiple sclerosis, study their function and how they together with life-style risk factors for multiple sclerosis interact.

Our research

We are trying to identify novel genetic risk variants for multiple sclerosis, both in collaboration with international consortia (e.g. International Multiple Sclerosis Genetic Consortium http://www.imsgenetics.org/) and more recently together with deCODE. We are using both traditional genotyping and next generation sequencing in these studies. Currently more than 200 susceptibility variants have been identified for multiple sclerosis, the major ones being in the HLA region. We are attempting to identify which genes these variants control expression for using RNAseq data from samples from multiple sclerosis patients.

We are studying how genetic multiple sclerosis risk variants interact with multiple sclerosis risk life-style exposures such as smoking, and viral infections since this pinpoints which biological processes are acting together to cause multiple sclerosis. We have so far identified several such interactions.

Immune response to viral infections such herpes virus infections (Epstein Barr and Cytmegalo Virus) is altered in multiple sclerosis, it is however unclear if this is a consequence of the disease or if these viral infections themselves affect the risk of developing MS. We are trying to address this by comparing genetic risk factors for serological response to these infections and genetic risk factors for multiple sclerosis.

Because we have access to a uniquely large and well characterized dataset of multiple sclerosis patients we are now embarking on trying to identify genetic and life-style exposure risk factors for progression/severity of multiple sclerosis. One of the stumbling blocks here is how to measure severity and progression. We will use a variety of measures ranging from standard measures such as EDSS, to patient reported outcomes and potential biomarkers such as neurofilament light. This work will be carried out in the MultipleMS project, a Horizon2020 funded project that is coordinated by Ingrid Kockum and Maja Jagodic. In this project we will also aim to stratify patients based on genetic and life-style exposures with the aim of identify subpopulations of patients that respond differently to different treatments in order to achieve personalized medicine for multiple sclerosis.

Research projects

  • MultipleMS: Multiple manifestations of genetic and non-genetic factors in Multiple Sclerosis disentangled with a multi-omics approach to accelerate personalised medicine
  • Role of virus infections in risk for multiple sclerosis
  • Genetic control of immune response to viral infections with focus on herpes viruses and JC virus
  • Functional analysis of genetic variants associated with multiple sclerosis.
  • NeurInox (http://www.neurinox.eu/): association NADPH oxidase genes (NOX) to severity of multiple sclerosis

Selected publications

Anoctamin 2 identified as an autoimmune target in multiple sclerosis.
Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjöberg R, et al
Proc. Natl. Acad. Sci. U.S.A. 2016 Feb;113(8):2188-93

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis.
Goris A, Pauwels I, Gustavsen M, van Son B, Hilven K, Bos S, et al
Brain 2015 Mar;138(Pt 3):632-43

JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.
Sundqvist E, Buck D, Warnke C, Albrecht E, Gieger C, Khademi M, et al
PLoS Pathog. 2014 Apr;10(4):e1004084

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
, Beecham A, Patsopoulos N, Xifara D, Davis M, Kemppinen A, et al
Nat. Genet. 2013 Nov;45(11):1353-60

Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis.
Hedström A, Sundqvist E, Bäärnhielm M, Nordin N, Hillert J, Kockum I, et al
Brain 2011 Mar;134(Pt 3):653-64

Group members

Rasmus GustafssonAssociated, Postdoc
Alexandra GyllenbergResearch coordinator
Jesse HuangPhD student, Graduate Student
Tojo JamesPhD student, Graduate Student
Izaura LimaAssociated
Ingrid Skelton KockumResearch team leader, Professor
Pernilla StridAssistant professor
Katarina TengvallPostdoc

Clinical Neuroscience