Genetic Effects Are Influenced by Lifestyle

The risk for developing obesity is influenced by our lifestyle as well as by our genes. In a new study from Uppsala University, researchers show that our genetic risk for obesity is not static, but is influenced by our lifestyle.

genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

In the current study, researchers have investigated if genetic effects are influenced by different lifestyle factors such as diet, smoking, socio-economic status, alcohol consumption and physical activity. The study builds on genetic and self-reported lifestyle information from 360,000 middle-aged people in the UK.

“The results of our study clearly show that the environment and the lifestyle interact with the genes,” says Mathias Rask-Andersen, researcher at the Department of Immunology, Genetics and Pathology, who led the study.

For example, the effect of genetic factors was lower in the most physically active participants. Socio-economic status also influenced the genetic effects. The genetic risk for obesity was more pronounced in participants with lower socio-economic status than in participants with higher socio-economic status. One of the most surprising results of the study was that alcohol consumption also influenced the genetic effects. The researchers could clearly see that the genetic effects were lower among those with more frequent alcohol intake. The genetic effect was nearly half as strong in participants who consume alcohol every day compared with never-drinkers.

The results suggest that we can influence our genetic risk by changing our lifestyle. Someone with a strong predisposition for obesity, for instance a person with many overweight relatives, could reduce the effect of their genes by making lifestyle changes. The hope is that the results of this study will lead to new angles of approach to understanding the mechanisms that regulate body weight and to better methods of treating and preventing obesity and overweight. However, it is important to point out that the current study is a population-based study. In such a study, the researchers are unable to assess cause and effect.

“There could be related factors that we do not have information about, which are the real causes of our results. It is therefore important to follow up on our results with more controlled studies to determine cause and effect,” says Mathias Rask-Andersen.

The study has been published in the scientific journal PLOS Genetics.

Source : Uppsala University