For more than ten years, lung researchers and epidemiologists at the Helmholtz Zentrum München have been investigating genetic factors associated with lung function and lung diseases within the framework of international consortia. Now they collaborated in a study that was recently published in ‘Nature Genetics’ and were able to show why people with smaller lungs have a higher risk of developing lung diseases. The genetic information revealed by this study can be translated into clinical practice to improve the prediction for the risk of chronic obstructive pulmonary disease (COPD) and to develop new approaches for treatment.
Researchers in the SpiroMeta consortium have been working for years to determine numerous areas in the genetic material that play a role in lung function. The group headed by Prof. Dr. Holger Schulz, acting Director of the Institute of Epidemiology I (EPI I) at the Helmholtz Zentrum München, has been involved since the beginning. “Since the project started in 2007, we have been able to expand our knowledge regarding lung-relevant genes substantially,” Schulz says in retrospect. “We are highly interested in the association between certain genes and lung function, since it is known that people with healthy but smaller lungs have a higher risk of developing lung diseases.”
World’s biggest study regarding genetics of lung health and disease
The consortium’s current work, in which the Helmholtz scientists are again involved, produced genetic evidence of why this might be. Dr. Christian Gieger, head of the Molecular Epidemiology Research Unit (AME) at the Helmholtz Zentrum München, explains: “We were able to identify genetic variants that are associated with lower lung function and increase the risk of developing COPD. This new and world’s biggest study regarding genetics of lung health and disease has also supplied the first pathophysiological explanations for the association between pulmonary function and certain genes.” These genes are furthermore candidates for innovative approaches to treatment. This translational aspect is especially important to the researchers.
Dr. Stefan Karrasch, scientist at the EPI I and likewise involved in the study, describes the methodological procedure. “First we examined the genome data from almost 49,000 persons with widely varying pulmonary function levels. The genetic variants found here were then followed up in a second stage that was based on the data of a further 95,000 subjects.”* This allowed the scientists to increase the number of variants from 54 to 97. The scientists hope that in the future, it will be possible to intervene at these points in the lung biology in order to battle diseases. Active substances are already being developed for some areas, according to the authors of the work, which was conducted under the aegis of the University of Leicester (please find the respective press release here). The scientists furthermore developed a risk score** in order to predict the probability of COPD development. Patients with the highest scores had an almost four times greater risk of developing COPD than those with the lowest scores.
* The data originated in the so-called UK Biobank. This large-scale project collects health data from 500,000 volunteer participants in the United Kingdom in order to improve the prevention, diagnosis and treatment of numerous illnesses. These also include, for example, diabetes, dementia, cancer and other widespread diseases.
** In medicine, the word “score” refers to the number of points that result from the various diagnostic parameters. It is used to assess a disease’s severity.
107 researchers from 14 countries participated in this study. This includes the Institutes of Epidemiology, Genetic Epidemiology, Molecular Epidemiology and Lung Biology and Disease/Comprehensive Pneumology Center at the Helmholtz Zentrum München, a partner in the German Center for Lung Research (DZL). Also involved from the German side were the Ludwig-Maximilians-Universität Munich and the Ernst Moritz Arndt Universität Greifswald.
The Munich based scientists mainly analysed the data from the Augsburg based KORA study: For almost 30 years, the Cooperative Health Research in the Region of Augsburg (KORA) has been examining the health of thousands of citizens in Augsburg and environs. The aim of the project is to increase understanding of the impact of environmental factors, behaviour and genes on human health. The KORA studies focus on matters relating to the development and progression of chronic diseases, in particular myocardial infarction and diabetes mellitus. To that end, research is conducted into risk factors arising from lifestyle factors (including smoking, diet and exercise), environmental factors (including air pollution and noise) and genetics. Questions relating to the use and cost of health services are examined from the point of view of health services research.
Wain, L. et al. (2017): Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. Nature Genetics, DOI: doi:10.1038/ng.3787
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.
The Institute of Epidemiology I (EPI I) conducts research into the significance of environmental and lifestyle factors, genetic constitution and metabolism in the genesis and progression of respiratory, metabolic and allergic diseases, as well as of selected types of cancer. Research is based on data and biological samples obtained from the population-based cohort studies GINI, LISA and MONICA/KORA. The Institute plays a leading role in the planning and setting up of the national cohorts.
The Research Unit of Molecular Epidemiology (AME) analyses population-based cohorts and case studies for specific diseases, using genomics, epigenomics, transcriptomics, proteomics, metabolomics and functional analyses. The aim of this research unit is to decipher the molecular mechanisms of complex diseases like type 2 diabetes or obesity. The unit administers the biological specimen repository of the Department of Epidemiology and stores the samples for national and international projects.
The Comprehensive Pneumology Center (CPC) is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität Clinic Complex and the Asklepios Fachkliniken München-Gauting. The CPC’s objective is to conduct research on chronic lung diseases in order to develop new diagnosis and therapy strategies. The CPC maintains a focus on experimental pneumology with the investigation of cellular, molecular and immunological mechanisms involved in lung diseases. The CPC is a site of the Deutsches Zentrum für Lungenforschung (DZL).