Genes and environment in PD – PhD interview with Kajsa Brolin
Kajsa Brolin explores how our genes and environment affect the risk of developing Parkinson’s disease. March 27, she defends her Ph.D. project partly based on MultiPark’s biobank sample collection. Here, she tells about the newly discovered genetic risk factor that might be specific to people in the southern part of Sweden. And is coffee really protective?
Tell us about your research!
“My research is about studying why some people get Parkinson's disease while others don't. Therefore, I primarily study genetics and how certain genes are linked to the disease, but I also look at lifestyle and exposure to various environmental factors such as tobacco use. By studying genetic and non-genetic factors in Parkinson's, we can contribute to understanding and identifying biological processes that may constitute potential drug targets in the development of future treatments.
In my main project, I have mapped both genetic and non-genetic risk factors for Parkinson's disease by using data from the "Multipark’s biobank sample collection" (abbreviated MPBC). The sample collection consists of approximately 1,000 people with a Parkinson's diagnosis and 1,000 without the disease ("controls"), where patients and controls have been matched on sex, year of birth and residential area. In the study, we have confirmed previous reports about links between the disease and exposure to environmental factors such as pesticides. We have also confirmed several genetic risk factors for the disease.
In addition to my main project, I have carried out both national and international collaborations where I participate in studies to understand how our genes affect the development and progression of Parkinson's disease and the REM sleep behavior disorder (RBD) which is associated with Parkinson’s disease.”
What did you discover?
“Interestingly, we discovered that a genetic risk variant, PLPP4, was linked to a (slightly) increased disease risk that has not been seen before. We believe this variant may be population-specific in the southern parts of Sweden.
Taken altogether, I think that the most important insight of my Ph.D. project has been that the etiology of Parkinson’s disease is very complex and that populational factors may be more important than previously thought. As some genetic variants are very rare, we do need international collaborations, but to solely rely on a few big cohorts is risky since ethnicity may play a pronounced role for certain subtypes of the disease, and to catch these differences, we need to have greater diversity among studies.”
How significant contributor is the PLPP4 locus?
“It is too early to know the impact of this genetic variant as it has, so far, only been seen in our cohort and another cohort from Oslo. This implies that we must access regional differences even within the same country. And that is also why biobanks collected from populations in different locations around the globe are needed. Among those who carry the genetic variant, the risk of developing Parkinson’s disease increases by around 30-40 %, according to our results. PLPP4 is a phosphatase involved in lipid signaling and Parkinson’s disease has been suggested to be a so-called lipidopathy, driven by dysfunctions in lipid signaling, but this remains to be elucidated.”
What are most important risk factors for PD, genetic or environmental?
“We still do not know this, but I think that environmental factors are in general contributing more and likely play an important role in the increase that is seen worldwide for the prevalence of the disease. For example, in China, there seems to be quite an increase in the prevalence of Parkinson’s disease. This coincides with their industrialization and the fact that air pollution has increased dramatically in the last decades and air pollutions has been suggested to be an emerging risk factor for Parkinson’s disease. Hence, environmental factors seem important for disease development. Modifying environmental factors is probably also easier and could potentially help slow down the increased prevalence rates. Still, we need to increase our understanding about multifactorial contribution through the carriage of different genetic risk variants combined with environmental exposures.”
Why is coffee “protective”?
“We have not investigated the potential molecular reasons behind the fact that Parkinson’s disease is associated with lower consumption of coffee, even though we could confirm this relationship in our biobank. These kinds of associations between lifestyle habits and the risk of getting a disease are always complicated to interpret. It may be because individuals pre-disposed to developing the disease already have a lower level of dopamine within their brain circuits related to reward. Hence, they would not get the same sense of pleasure when consuming coffee and, therefore, might consume less. But this, we still don’t know, so researchers will have to look more into this experimentally.“
What difference could your project make for patients?
”Most people want to know why they get this, so far, incurable disease. Even if they still cannot be cured with the knowledge we have today, it may offer some answers that could relieve some of their concerns and help them accept their condition. I also think that we have a responsibility to use the material we collected from so many participants to offer them some answers and contribute with new knowledge.”
How did you end up at MultiPark?
"When looking for thesis projects for my master's thesis, I searched for a project in neuroscience focusing on epidemiology. I had Maria Swanberg as a lecturer in a course during my bachelor's education, and by chance, I found a suitable project with her! Maria is affiliated with MultiPark and the coordinator of the MultiPark’s Biobank sample collection MPBC. After my master's project, I was offered to continue as a doctoral student and work further on the project."
What have you most appreciated so far during your time as a PhD student at MultiPark?
“Being part of a fantastic network with many talented researchers. In particularly, I have appreciated our lunch seminars within the doctoral education (Neuroscience graduate school seminar series), where you have been able to learn about the research of other doctoral students and meet others within Multipark to discuss research.”
What have been the most challenging during your Ph.D.?
”To find people with the knowledge I needed to gain to carry out the analyses. Eventually, I found professional networks to increase my understanding of bioinformatics and handling this kind of data.”
And the most rewarding?
“That we finally got usage of the fantastic biobank material we have. And to show the insights we got to the participants contributing to the sample collection.”
What advice do you want to give to new Ph.D. students?
“Dare to ask for help! No questions are stupid; everybody started from scratch.”
What happens after your defence?
“I will stay in Mara Swanberg’s research group, Translational neurogenetics, until the summer.”
Fast five with Kajsa Brolin
“My fiancé Erik and our dog Viggo”
“I sing in a choir”
Best time of your day:
“I am a “lagom” person, no early mornings, no late evenings, daytime is perfect”
IPDGC (International Parkinson’s Disease Genomic Consortium) meeting in London 2019
Need help with:
How to write a non-academic CV
Ph.D. Student at Translational Neurogenetics
kajsa [dot] brolin [at] med [dot] lu [dot] se