New clues about why non-smokers, as well as smokers, develop chronic lung disease revealed

A group of researchers led by the Universities of Leicester and Nottingham has discovered genetic differences that put some people at higher risk than others of developing chronic lung disease.

The new study, published in Nature Genetics, shows that genetic differences help explain why some people who have never smoked develop chronic obstructive pulmonary disease (COPD), and why some smokers are at higher risk of getting the disease than other smokers.

During the two-year study, researchers measured 20 million differences in the DNA in each of the 400,000 people who took part and compared them to measurements of lung function taken from breath tests. The results found 139 new genetic differences that influence lung health and COPD. These differences increase someone’s risk of developing COPD, in addition to smoking.

COPD is a life-limiting lung condition which causes increasing breathlessness due to damage to the airways. Although smoking greatly increases a person’s risk of developing COPD, 1 in 5 people who have the disease have never smoked.

Professor Ian Hall, Director of the Nottingham Biomedical Research Centre, said: “We have shown how close working between the NIHR Biomedical Research Centres in Leicester and Nottingham, together with our international collaborations, enables powerful research to improve future healthcare.

“The most important measure to prevent COPD in the UK is to avoid smoking. All smokers can reduce their risk of developing COPD by quitting smoking. Reducing exposure to high levels of air pollution is also likely to be beneficial. Patients who already have COPD need new treatments. We are delighted that our research has brought this a step closer.” 

Professor Louise Wain, British Lung Foundation Professor of Respiratory Research at the University of Leicester and lead author of the study, said: “It is well established that smoking is a major risk factor for COPD, yet the mechanisms which cause smokers and non-smokers alike to develop COPD are poorly understood. Our study provides vital clues as to why some people develop COPD and others don’t, and new knowledge that will help to develop new treatments to halt the decline in lung function observed in patients with COPD.”

The researchers divided people into 10 different genetic risk groups, depending on the number of DNA differences shown to affect lung health. 8 out of 10 smokers in the highest genetic risk group develop COPD. People who have never smoked were overall at very much lower risk, but around 2 in 10 non-smokers in the highest genetic risk group still develop COPD. In all, 279 differences in the DNA were found to affect lung health and the risk of COPD.

Professor Martin Tobin, Chair of the Leicester Precision Medicine Institute, a partnership between the University of Leicester and Leicester’s Hospitals, and co-lead author of the study, added: “We are closer to understanding the genetic causes of this condition in people who have never smoked. People who smoke also appear to have a similar pattern of genetic risk factors, alongside the added risk of tobacco smoking. Our findings can help in developing new treatments that will benefit both groups.

“These advances would not have been possible without the generosity of the participants in UK Biobank and in the international research projects that also contributed to this research.”

The team were able to show that the genetic differences they identified were also important contributors to COPD risk in other ethnic groups, including African American and Chinese populations. COPD affects 250 million people and is responsible for 5 per cent (or approximately 3.1 million) deaths worldwide every year. If the genetic differences identified in this study can be used to develop new treatments, these could impact on global health.

The research was supported by the Wellcome Trust, the Medical Research Council, the British Lung Foundation and the National Institute for Health Research (NIHR).

The study 'New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries' is published in Nature Genetics today Monday 25th February 2019: https://doi.org/10.1038/s41588-018-0321-7.

More information about COPD statistics for the UK: https://statistics.blf.org.uk/copd 

WHO information: http://www.who.int/en/news-room/fact-sheets/detail/tobacco http://www.who.int/en/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)

Ends

More information is available from Professor Ian Hall, NIHR Nottingham Biomedical Research Centre, University of Nottingham via email ian.hall@nottingham.ac.uk, Professor Louise Wain louisewain@leicester.ac.uk, Professor Martin Tobin mt47@leicester.ac.uk or Emma Rayner/Emma Thorne in the Press Office on +44 (0)115 748 4413 or emma.rayner@nottingham.ac.uk  Emma.thorne@nottingham.ac.uk +44 (0)115 951 5793

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Notes to editors:

The University of Nottingham is a research-intensive university with a proud heritage, consistently ranked among the world's top 100. Studying at the University of Nottingham is a life-changing experience and we pride ourselves on unlocking the potential of our 44,000 students - Nottingham was named both Sports and International University of the Year in the 2019 Times and Sunday Times Good University Guide, was awarded gold in the TEF 2017 and features in the top 20 of all three major UK rankings. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement. We are ranked eighth for research power in the UK according to REF 2014. We have six beacons of research excellence helping to transform lives and change the world; we are also a major employer, proud of our Athena SWAN silver award, and a key industry partner - locally and globally.

About the University of Leicester

The University of Leicester is led by discovery and innovation – an international centre for excellence renowned for research, teaching and broadening access to higher education. It is among the top 25 universities in the Times Higher Education REF Research Power rankings with 75% of research adjudged to be internationally excellent with wide-ranging impacts on society, health, culture, and the environment. The University is home to just over 20,000 students and approximately 3,000 staff.

Find out more: https://le.ac.uk/about

About the Wellcome Trust

Wellcome exists to improve health by helping great ideas to thrive.

We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. 

We are a politically and financially independent foundation.

About the Medical Research Council (MRC)

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. www.mrc.ac.uk

About the British Lung Foundation

The British Lung Foundation is the only UK charity fighting to help the 1 in 5 people in the UK affected by lung disease, by researching new treatments, campaigning for better awareness and services, and providing support and advice for patients, carers and family members. Read more about what we do, follow us on Twitter or join us on Facebook.   

About UK Biobank
This work was under taken using the UK Biobank resource. www.ukbiobank.ac.uk

About NIHR Leicester Biomedical Research Centre

The National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (BRC) is a partnership between University Hospitals of Leicester NHS Trust, the University of Leicester and Loughborough University. It is funded by the National Institute for Health Research (NIHR).

The NIHR Leicester BRC undertakes translational clinical research in priority areas of high disease burden and clinical need. These include cardiovascular disease, respiratory disease, and lifestyle, obesity and physical activity. There is also a cross-cutting theme for precision medicine. The BRC harnesses the power of experimental science to explore and develop ways to help prevent and treat chronic disease. It brings together 70 highly skilled researchers, 30 of which are at the forefront of clinical services delivery. By having scientists working closely with clinicians, the BRC can deliver research that is relevant to patients and the professionals who treat them. www.leicesterbrc.nihr.ac.uk

The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. www.nihr.ac.uk/patientdata

About NIHR Nottingham Biomedical Research Centre

The NIHR Nottingham Biomedical Research Centre (BRC) is improving the health of millions of people with common diseases like asthma and arthritis. We drive innovation in experimental science and translate research into breakthrough treatments, innovative technologies and new medicines. Our world-leading research is in: 

• hearing • gastrointestinal and liver disorders • musculoskeletal diseases • mental health and technology • respiratory diseases • Magnetic Resonance Imaging (MRI) which supports all areas of research

The NIHR Nottingham BRC is a partnership between Nottingham University Hospitals NHS Trust and the University of Nottingham, supported by Nottinghamshire Healthcare NHS Foundation Trust and Sherwood Forest Hospitals NHS Foundation Trust. It is funded by the National Institute for Health Research (NIHR) – the research arm of the NHS.

March 2019

Posted on Friday 15th March 2019