Karolinska Institutet

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Twins – An Important Epigenetic Tool

An important part of my work is to carefully plan my studies so that we actually measure what we intend on measuring and nothing else. Maybe this sounds straightforward but it’s not quite that easy.

As an epigeneticist, I study the impact of the environment on the genome (read more here). What makes it all difficult is that our epigenome is not static, but constantly exposed to changes from our environment. For example, if we discover an epigenetic difference between sick and healthy people, we cannot say whether the difference seen  is the cause of the disease or a consequence of it. In most cases we are studying people who are already sick. And, to make things all the more complicated, most diseases are the result of a combination of heritage and the environment.

So how do we get around around this? There are a few different ways to design a study to filter out the noise of unwanted signals, and clarify what is cause and effect. One way to sort out the noise from our genes and just study the environmental impact is to use twins. Identical twins have the same genome and to some extent a common environment, however, the older they get the more separated their living environment and habits tend to become. And this is what we benefit from when studying twins where only one twin has suffered from a particular disease.

In one of our studies, we studied epigenetic changes and rheumatic disease with the help of identical twins from the Swedish Twin Registry. And to find out more about the onset of the disease, and not just the effect, we also studied “healthy” twins who have not yet been affected by rheumatism, but who are likely to develop the disease as they have a certain type of antibody in their blood that is associated with rheumatism (antibodies against ACPA).

With this approach, we were able to identify methylation differences that were not dependent on the interference of the genes. But why do you want to do this? Well, in the vast majority of studies that investigate rheumatism, a certain group of genes pop up, the so-called HLA genes. These genes encode proteins that help our immune system talk about what is body-like or body-foreign.

The HLA genes are involved in one way or another in rheumatism, and also in many other autoimmune diseases. But, with the help of identical twins, we could identify other genes involved in addition to the HLA genes. The PCDHB14 gene was found to be differently methylated in both the “healthy” twins with ACPA antibodies in their blood and the diseased twins, suggesting that this gene is involved in the actual development of the disease.

PCDHB14 belongs to a large complex gene family that is mainly expressed in the brain and which has been reported to be involved, just like the HLA genes, in sensing what is own and body foreign. Super interesting! In the mentioned study, we could not point out which environmental risk factor or factors could possibly be behind the development of the disease, but we gained knowledge about which biological systems could be involved in rheumatism. One puzzle piece at a time!

In another study, we focused instead on one of the most common risk factors for many autoimmune diseases, namely smoking. We wanted to investigate how smoking affected MS patients and then looked at smokers, former smokers and MS patients who had never smoked. But I’ll tell you more about this in my next post here at Food Pharmacy.

Louise Sjöholm has a education in molecular biology and a doctorate in depression genetics from Karolinska Institutet. She has been working as an epigeneticist for seven years and is researching the role of the gastrointestinal tract in autoimmune diseases, i.e., diseases in which the body’s immune system attacks its own tissue. She is also interested in understanding the epigenetics of bacteria and its connection to health and disease. The views in the chronicle are the writer’s own.

Photo by Sharon McCutcheon on Unsplash



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