Are you at Risk? – Predisposing factors for diseases

At some point of our life, we all have wondered – Am I at risk? Why does someone get disease and how come the symptoms are so different among those with the same illness? The 19th Science Day of the Kontinkangas delves into this intriguing subject. The event is organized on February 22nd, 2022 jointly with the Faculty of Medicine and the Faculty of Biochemistry and Molecular Medicine at the University of Oulu.
Picture: Sonja Salmi

Many of the disease predisposing factors are related to life-style choices seemingly controllable by ourselves, such as nutrition, exercise, and sleep, as well as alcohol and tobacco use. But is it really that simple? There are a lot of factors we cannot control, or we can only control to some extent, starting from our genes to socio-economic status, disease predisposing pathogens we’re exposed to, as well as childhood experiences. Even the living conditions of our parents may influence our predisposition to diseases. How do these factors affect our ability to make life-style choices beneficial for our health? The risks of diseases, in the hub of this complex network, without doubt fascinate scientists all over the world. For this blog, we asked the researchers at the University of Oulu to give us a peek to their research and share their views on the subject.

We encounter numerous risk factors in our lives, some of which are dynamic and may change during our life-course. Professor Sylvain Sebert conducts research at the Center for Life Course Health Research, Faculty of Medicine. His group is involved in European network of life-course cohorts and longitudinal studies including for example LifeCycle, EarlyCause, EucanConnect and LongITools: “We aim at elucidating the life-course development of chronic cardiovascular and mental diseases and identify how the heritable components - genes and the epigenomes, interplay with the exposome, which mean a sum of pluri-environmental factors.”

The research should be more inclusive

Professor Sebert highlights the huge steps that scientific community has taken to substantially improve the understanding of the disease predictive factors: “For the last decades, thanks to the human genome project we’ve gained immense amount of knowledge on the predisposing factors to chronic diseases such as type 2 diabetes, obesity or depression, but also on non-biological phenotypes such as education or social factors. With such knowledge we can predict variations in weight, height, BMI with a fairly good precision.” However, he reminds that this does not predict health. “We must work on multiple fronts to be able to action this knowledge into active and ethical health promotion”, he says.

He also points out, that the research has to be carefully conducted and interpreted: “First, the research must be more inclusive including and understanding the role of ethnicity and sex”. He reminds us that most of the genetic data used in research is from white European descent. “Second, while the predisposition is still viewed as the bullet, the causal factor, we must understand the environmental trigger, including the timing and the interaction with the context; on the other words: who, when and where.” It seems the research in disease predictive factors is far more complex than one would think. But luckily, enthusiastic researchers don’t hesitate to take the challenge!

Adopting healthy lifestyle should be possible for all of us, but do we all have equal starting points to keep in track to promote our health?

Personality may play a significant role in disease predisposition

Professor of Psychology Mirka Hintsanen from the Faculty of Education brings in the often-forgotten factor that may determine our behavior and thus, our health: “It is well-known that health behaviors like sedentary life style, smoking and alcohol consumption may predispose us to health problems. It is less often noted that individual differences in our personality may affect our tendency to adhere to healthy behaviors.” According to Professor Hintsanen, personality may play quite a remarkable role in disease predisposition, although in a highly complex way: “Personality does not define whether we have unhealthy habits, but it may increase our risk for them. Personality traits, like the big five traits: extraversion, emotional stability, agreeableness, openness, and conscientiousness, are stable individual differences in how we tend to feel and behave.

Personality traits may predispose us to health problems also through several other routes than health behaviors: For instance, personality traits may increase our tendency to feel stress. Stress in turn increases risk for many diseases. Effects of personality to sleep and social support are also among the potential pathways similarly to tendency for risk taking and tendency to follow, or not to follow, doctor’s orders. Sleep problems, low social support, and tendency not to adhere to treatment instructions predispose us to diseases. High risk-taking behavior may lead for instance to traumatization or sexually transmitted diseases. All major personality traits have been associated with increased or decreased disease risk.”

Seems like we are to some extent defined by our personality on how we can cope with, for example, stress and sleep – the factors we all know may affect our health dramatically when unbalanced. The personality instead is, at least partially, built up from our earlier experiences but also from the traits we inherit in the form of genes.

Uncovering the genetic background of breast cancer

The secrets of genes have become familiar to Academy Research Fellow, Docent Katri Pylkäs from the Faculty of Medicine as she has been working for years to find the predisposing factors of breast cancer: “Being a woman and getting older are the main risk factors for breast cancer. Based on the familial clustering of the disease about 10% of all cases are estimated to also have a strong genetic component. So far identified inherited gene mutations explain about half of the familial cases.”

But again, it is not the whole story and as Dr. Pylkäs brings up, further research is needed: “Additional clinically relevant predisposition alleles are expected to be revealed by the increasing use of constantly developing genomic analysis methods. These include massive parallel sequencing for the detection of nucleotide level mutations and novel high-resolution imaging techniques than can reveal larger genomic structural variants related to disease predisposition.”

The future opportunities for research do seem fascinating as the methodologies develop and hence, we will probably continue to increase the knowledge on the predisposing factors.

Environmental and genetic factors contribute to the development of psychosis

Professor Juha Veijola from the Faculty of Medicine brings up the importance of method development in improving our understanding of both the disease and its predisposing factors: “The development of schizophrenia and other psychotic disorders are caused by a complex and multifactorial progress in the brain structure and functions. In the 70’s computed tomography, shortly CT, revealed that brain ventricles were larger in people with schizophrenia compared to healthy control participants. Since then, the topic of abnormalities in the brain structure and functions in psychosis has been under intensive research.”

He mentions that The Oulu Brain and Mind research team has contributed to the field for 15 years with fascinating findings: “One aim of the brain studies in psychotic disorders is to detect specific brain changes before the onset of first episode of psychosis. Specific findings would enable development of intervention methods to prevent the onset of psychosis. The Oulu Brain and Mind study has been able to explore structural and functional changes with the help of magnetic resonance imaging, shortly MRI, in people at genetic or symptomatic risk for psychosis. Both minor structural and functional brain abnormalities have found.”

Professor Veijola also gives a flash about the yet less explored factors in psychosis: “Future research will include research of environmental factors affecting brain functions. There are multiple environmental predisposing factors along with genetic factors contributing to the development of psychosis. The environmental factors include obstetric complications, minority status in the society, traumatic childhood experiences and use of cannabis.”

The awareness of individual risk factors can be beneficial

Why is it so important to identify the risk factors for diseases? Although the awareness of a risk for an individual might be stressful, it can also help to avoid or cope with triggering factors or to improve the treatment, and sometimes even prevent the disease.

Dr. Pylkäs knows that in case of breast cancer, the awareness of risk factors can be highly beneficial and save lives: “Surveillance makes it possible to detect cancer at an early stage when it is most likely to be curable. In the case of high-risk mutations, such as those in BRCA1 or BRCA2 genes, even prophylactic surgeries can be an option. These decrease cancer risk substantially.”

Moreover, Dr. Pylkäs’s research on genetic risk factors may help the development of treatments: “Increasing knowledge about predisposing genes, and the cellular pathways affected by their mutations, helps to understand the etiology of breast cancer. This can also reveal therapeutic vulnerabilities of the tumors related to specific gene mutations.”

Presumably, we will hear more about the exciting outcomes of these and numerous other ongoing research projects on disease predisposing factors conducted at the University of Oulu. Hopefully, the awareness of our personal risk factors would not only provide us with better and preventive health care but also could guide us to take better control over our own health. We absolutely agree with Professor Sebert’s wise words: “The future is exciting, and predisposition will play a very important role as long as we understand that we do not only inherit the genes of the previous generations, but we also inherit the context, like environment and the social factors, to change it.”

Pirjo Åström, PhD is biochemist and researcher at the University of Oulu, Faculty of Medicine. Her research focuses on examining novel potential susceptibility genes and the biological mechanisms in diseases related to defective immune system.

Docent Salla Ruskamo studies 3D structures, lipid-protein interactions and disease-linked isoforms of neuronal proteins. She works in the Protein and Structural Biology Research Unit and is specialized in myelin integral proteins and proteins associated to myelinopathies.