Global Biobanks Collaboration Identified Novel Gene Variants for a Rare Severe Lung Disease

A Finnish-led international research team has discovered novel gene variants that increase the risk of a rare but severe lung disease, idiopathic pulmonary fibrosis. The results also demonstrate notable genetic similarities with susceptibility to severe COVID-19 infection.

Global Biobanks Collaboration Identified Novel Gene Variants for a Rare Severe Lung Disease
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The study, led by the University of Helsinki, identified seven previously novel genetic risk factors for idiopathic pulmonary fibrosis. Only one of these would have been identified if the study had utilized data from European biobanks only.

Global collaboration enabled the study involving nearly 1.4 million people of six different ancestries from around the world, including more than 11,000 idiopathic pulmonary fibrosis patients.

“Most of the risk genes we have now identified are completely new and their function in the lung is unknown, while others appear to be related to lung function, such as lung function measures or mucus secretion,” says Juulia Partanen, PhD researcher at the Institute for Molecular Medicine Finland FIMM, University of Helsinki, who was the first author of the study.

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International cooperation is a prerequisite for studying a severe rare disease

Large-scale genetic studies have proven to be an effective way of acquiring insight into disease mechanisms. They allow the identification of genetic risk factors that influence disease susceptibility and thus biological pathways relevant to disease.

However, for rare diseases, the challenge of genetic analyses is the small number of patient samples available. To obtain reliable results, typically thousands or even tens of thousands of patients are needed and therefore global collaboration is essential, especially for rare diseases.

Idiopathic pulmonary fibrosis is a severe scarring disease of the lungs for which there is no curative treatment. The unknown cause of the disease makes genetic studies of the disease particularly interesting, as they may shed light on the mechanisms underlying the disease, thus providing hints for new treatments.

The number of patients with idiopathic pulmonary fibrosis in Finland is estimated to be around 1000. Given the small number of patients, international collaboration and pooling of data collected in different countries proved crucial both in terms of sample size and the genetic diversity of the subjects.

“A key factor in the success of the study has been the persistent work of Finnish pulmonologists on behalf of patients with pulmonary fibrosis and the positive attitude of patients towards biobank studies. This has made it possible to collect unique clinical data and conduct biological studies,” says Professor of Lung Diseases and Allergology Marjukka Myllärniemi, Chief Physician at the Helsinki University Hospital.

In this study, the researchers drew on 13 biobank studies from around the world, including the Finnish FinnGen study. In this way, the number of patients enrolled in the study more than quadrupled compared to the largest study thus far.

“Genetics research has previously focused heavily on European populations. The current study shows that a significant proportion of genetic risk factors for disease will remain unidentified unless we actively seek to change this tradition. It is also globally equitable to extend research into the causes of disease to diverse populations. Such collaboration is only possible by openly sharing information between researchers,” says Jukka Koskela, Academy of Finland clinical researcher at the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki, who led the study.

Genetic similarities with severe COVID-19

The study also confirmed previous findings of shared genetic background between idiopathic pulmonary fibrosis and severe COVID-19 disease. A total of seven genetic risk factors for pulmonary fibrosis were also found to influence the risk of developing severe coronavirus disease.

“The exacerbation phase of pulmonary fibrosis shows lung damage somewhat similar to that seen in severe coronavirus disease. We have been wondering whether shared genetic regions are linked to this type of lung damage or whether there is something else that links the two diseases and whether there is some way to influence the development of the damage in the future,” says Juulia Partanen.