Scientists from Heidelberg University Hospital the German Cancer Research Center and the company Febit Biomed GmbH have now developed a method that facilitates the analysis and detection of disease-causing genetic modifications for the first time ever this method enables the genetic characterisation of cardiomyopathy patients. For patients and their relatives this means that the disease can now be reliably diagnosed and specific treatment and care be put in place at an early stage. In future it will also be possible to offer the new method to a larger number of patients than was previously the case.
Lysosomal storage diseases LSD are a group of around 50 rare inherited metabolic disorders. Only 12 LSDs have been described biochemically and microbiologically. Prof. Dr. Michael Przybylski from the Steinbeis Transfer Centre for Biopolymer Analysis and Proteomics at the University of Constance now hopes to change this situation. In a project carried out in cooperation with the biotech company Genzyme CEE Konstanz and the University of Timisoara Przybylski has developed two highly sensitive molecular methods involving mass spectrometry and fluorimetry and validated them for use in clinical diagnostics.
Dr. Kerstin Stemmer from the University of Konstanz has found a way to identify the carcinogenic potential of substances in just a few days using state-of-the-art technology and new investigation methods. This is the first time that researchers have been able to reduce the time and the number of animals used in carcinogenesis studies.
GATC Biotech AG is already on the lookout for next generation sequencing technologies in the form of real-time single-molecule sequencing. In an interview with BIOPRO Thomas Pohl CTO of GATC Biotech AG explains why the company is continuously expanding its existing equipment with the latest global technologies.
Hope for breast cancer patients under the leadership of the Vorarlberg Institute for Vascular Investigation and Treatment VIVIT a cross border cooperation is to start between hospitals and bioanalytical laboratories of the Rhine Valley and Lake Constance region. It is aimed at exploring the influence genetic material DNA has on the progression of breast cancer and the response to breast cancer treatment. A collaboration which became possible thanks to the BioLAGO association.
Researchers led by the Ulm paediatrician Holger Cario have identified a rare, congenital genetic defect that leads to the dysregulation of the folic acid metabolism, resulting in aenemia, epilepsy and learning difficulties in children. All aspects of the disease can be treated quite successfully with the exception of the cramps associated with the defect.
Around 3000 people suffer from achromatopsia in Germany. Achromatopsia is an inherited visual disorder characterised by the absence of full colour vision. The disease is caused by a genetic defect that makes the retina's cone photoreceptors, needed for daylight and colour vision, non-functional. There is currently no cure for achromatopsia. Scientists from Tübingen University Hospital and their colleagues from Munich and New York have now developed a gene therapy approach to treat the eye disease.
Rapid progress in sequencing technologies is poised to set the imagination of biomedical researchers on fire. Experts now believe that progress is about to make possible what seemed to be utopian a few years ago – it seems likely that it will soon be possible to sequence the human genome in only a few minutes and store and automatically analyse it using tiny automates. However, is everything that is technically feasible also reasonable?
The ability to detect a broad range of conditions and modifications in human, animal, plant and pathogen genes is highly important in the field of medicine for diagnosing diseases and starting therapy as quickly as possible. Chemists at the University of Konstanz have now developed a genetic test that does not need to be carried out in the laboratory and can be evaluated with the naked eye, similar to a pregnancy test. The test would therefore be suitable for rapid and simple on-site tests.
The Department of Cardiology at Heidelberg University Hospital and Siemens Corporate Technology have been working together since 2011 to develop new software that improves the diagnosis of heart diseases. The new software analyses and manages data related to the genetic causes of cardiomyopathy and presents the data to physicians in a clear manner. Specific microRNAs in the blood of patients have the potential of being used as new biomarkers, thus making diagnosis of a heart attack more rapid and reliable.
Hain Lifescience GmbH is a biotechnology company that develops, manufactures and distributes molecular genetic test systems and instruments. The company was established by brothers David and Tobias Hain in 1988 and employs over 100 people at its headquarters in the city of Nehren in the district of Tübingen. Hain Lifescience also has four subsidiaries abroad. The company focusses on the development of test systems for the early and rapid identification of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), which is the major cause of hospital-acquired infections. The company’s MRSA test provides a reliable result in less than three hours, enabling appropriate therapeutic measures to be taken rapidly.
Epigenetic DNA modifications have been shown to play a role in carcinogenesis and are therefore a promising target for the early detection of cancer. Dr. Daniel Summerer and his research group at the University of Konstanz have developed a method that enables the direct and site-specific identification of epigenetic changes. The method represents a new approach in the field of epigenetic analysis as well as a major step towards simpler cancer diagnosis.
The exome is the part of the genome that is formed by exons i.e. the DNA regions that code for proteins and other functional products. Though comprising only about 1 of the total genome the majority of disease-causing mutations occur in the exome. Selectively sequencing the coding regions of the genome is quicker than whole-genome sequencing. Therefore exome sequencing plays an important role in the diagnosis of genetic diseases and cancer. Konstanz-based GATC Biotech AG has designed InViewTM 1-Week Exome Diagnostic an exome sequencing service with the worlds fastest turn-around time.
The prostate genome project, which is part of the International Cancer Genome Consortium, is focused on the genetic and epigenetic causes of the development and progression of this highly variable cancer and finding markers that enable the reliable diagnosis of the disease. The German research groups involved in the project are coordinated by the German Cancer Research Center and concentrate on prostate cancer patients under 50 years of age, as these cases might be key to understanding the development of the disease.
Around 6,000 genetic diseases can be diagnosed using genetic tests. Genetic testing enables the accurate identification of diseases especially when symptoms are unclear, and also allows statements to be made about disease progression. However, restrictive regulations considerably hinder the use of genetic diagnostics. BIOPRO spoke with Dr. Dr. Saskia Biskup, a human genetics specialist and co-founder of the Tübingen-based company CeGaT.
In the new gene technology report, the interdisciplinary working group of the Berlin-Brandenburg Academy of Sciences (BBAW) takes stock of gene technology developments in Germany during the past few decades, and discusses the societal, legal and ethical challenges associated with these technologies in the future. The report is highly topical due to the controversy surrounding the ruling of the European Court of Justice on CRISPR/Cas9 genome editing.
A team of researchers from Freiburg has used direct programming to successfully produce kidney-like cells very similar to natural renal tubular cells in terms of appearance and function. These cells are thus a promising alternative to kidney cells isolated from animals and cells differentiated from embryonic stem cells. The reprogrammed kidney cells can be used, for example, for pharmacological and toxicological tests and investigating the disease mechanisms of genetic renal diseases.
Gene therapy approaches are increasingly being used for treating life-threatening diseases in humans. GeneWerk GmbH, a spin-off of the DKFZ and the NCT in Heidelberg, offers customised, high-resolution molecular and bioinformatic analyses that ensure the efficacy and safety of gene therapy and immunotherapy studies.
Watson and Crick deciphered the structure of DNA around 60 years ago and thus provided the key to understanding how genetic information is passed on. Since this discovery, which laid the foundation for molecular biology, new insights and developments have significantly changed many research areas and have also found their way into our everyday lives. DNA sequencing, genetic fingerprinting or personalised medicine – Watson and Crick’s heritage is omnipresent.
The quantitative detection of DNA single-strand breaks is of great importance for many areas of biomedical research and diagnostics. The Fluorescence-detected Alkaline DNA Unwinding FADU assay assists in the investigation of mechanisms of DNA damage and repair following DNA strand breaks upon exposure to chemicals. Prof. Alexander Bürkle and his team at the University of Konstanz have automated and optimised the original FADU assay which was published in 1981 to make it more efficient and quicker than before.
DNA sequencing has become indispensable in modern science. Innovative advances that will bring about changes in the life sciences and medicine are due to rapid developments in genome analysis technologies. In the interview below, Peter Pohl, CEO and co-founder of GATC Biotech AG, explains why DNA sequencing will become even more important in future.
In adults, cells such as nerve or cardiac muscle cells have lost the ability to regenerate. This is why myocardial infarction is so dangerous – damaged cardiac muscle cells do not grow back and scar tissue forms in their place. Prof. Dr. Gilbert Weidinger and an international team of researchers have deciphered a mechanism responsible for the regeneration of the zebrafish heart.
Ulm has long been a world leader in diagnosing and treating rare neurological disorders, notably amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Huntington's disease (HD). We spoke with Professor Albert C. Ludolph, spokesperson for the Ulm DZNE site, medical director of the Clinic for Neurology at the RKU (University and Rehabilitation Clinics of Ulm) and world-renowned ALS researcher.
The recent German Cardiac Society meeting in Mannheim in April 2012 focused on the latest findings related to the prognosis, diagnosis and therapy of heart diseases. While great progress has been made in the therapy of disease symptoms, it will still take a long time before gene and stem cell therapies that target the causes of disease find their way into clinical application. The conference also presented the new German Centre for Cardiovascular Research, which will be located at seven centres in Germany. The centre will specifically focus on the translation of research on the most important cardiac diseases (e.g. cardiac insufficiency) into clinical application and the pooling of expertise for the development of new therapies and diagnostics for the treatment of cardiovascular diseases.
Diagnosing suitable biomarkers is a prerequisite for tailoring personalised therapies to patient heterogeneity. Genetic tests and genome sequencing play a key role in these diagnoses. Up until now, personalised therapy has achieved the greatest success in the field of oncology. However, personalised treatments are also gaining in importance for treating other diseases.
Thanks to improved diagnostics and therapy, today’s cancer patients can live considerably longer than patients several years ago. Nevertheless, some cancers, especially the strongly metastatic ones, are difficult to treat. Therapies targeting immune cells or cancer stem cells could potentially improve the current situation. The early detection and classification of tumours is crucial for the successful treatment of the disease, and molecular diagnosis involving biomarkers and genome analyses are important for personalising cancer therapy.
Researchers from Heidelberg have shown that the organismal balance between heat production and energy storage is regulated by a gene called THADA. In animal experiments, knocking out the THADA gene leads to excessive food intake, obesity and sensitivity to cold. As humans spread throughout the world and settled in different climate zones, THADA was exposed to high selection pressure due to evolutionary adaptation. This explains why human susceptibility to obesity is more prevalent in warm climates.
Genetic testing is beginning to play an important role in personalised medicine and is indispensable for the diagnosis and therapy of many diseases. However, the preventive and diagnostic power of many genetic tests is still inferior to traditional diagnostic tests. In addition, commercial genetic tests do not always live up to the claims made about them.
IHO GmbH from Mannheim offers a professional solution for the international exchange of information and services concerning the molecular diagnosis of leukaemia. This drives forward the harmonisation of these methods and brings therapy monitoring to a new global level.
Therapeutic success can only be achieved when diagnoses are as precise as possible. Nowadays, genetic analyses can make precise diagnoses for many diseases. And thanks to high-throughput technology, results are available to patients very quickly. Dr. Dr. Saskia Biskup recognised the importance of precision medicine many years ago and went on to found CeGaT GmbH, a company that combines human genetics with high-throughput sequencing. Three subsidiaries have since been created and Biskup, a medical doctor by training, would under no circumstances give up her autonomy for a purely academic career.
CeGaT GmbH Center for Genomics and Transcriptomics in Tübingen is one of the first organisations that have managed to combine human genetic diagnostics with high-throughput sequencing for the diagnosis of specific tumour variants. CeGat researchers have developed diagnostic panels that they use to study more than 550 tumour-relevant genes simultaneously. The identification of genetic changes provides a more detailed diagnosis of tumours and helps doctors adapt therapy to the individual requirements of their cancer patients.
Scientists from the Center for Prenatal Diagnosis and Human Genetics, Kudamm-199, in Berlin have been working with scientists from GATC Biotech AG and LifeCodexx AG to develop a non-invasive diagnostic test based on Next Generation Sequencing which reliably detects a fetal trisomy 21 (Down syndrome).
Oesophageal cancer is a rare but highly aggressive type of cancer with a rather poor prognosis. Dr. Theresa Ahrens, a researcher in a group led by Prof. Dr. Silke Laßmann and Prof. Dr. Martin Werner at the Institute of Clinical Pathology at the Freiburg University Medical Centre, has tested a variety of epigenetic drugs that can interfere with the development of oesophageal cancer.
A protein in the nucleus of liver cells is produced in greater quantities when we go hungry; it limits fatty acid uptake and adjusts the metabolism in the liver. However in people with metabolic disorders, the abnormal expression of this protein (GADD45β), which was previously only known to be involved in the regulation of cell division and DNA repair, leads to a dysregulated fat and sugar metabolism. Scientists from the DKFZ and Helmholtz Zentrum München have now found out what happens at the molecular level when we go hungry and why periods of food deprivation may promote health.
Although the methods used to carry out amniocentesis are quite sophisticated, there is still a 0.5 percent risk of miscarriage following the intervention. Therefore, an EU-funded project called AngeLab is developing a rapid test that only requires a blood sample of the mother rather than amniotic fluid. The test yields information on the genetic health of the foetus within only a few hours. As part of the project, researchers from the Hahn-Schickard site in Freiburg have developed an innovative droplet PCR system.
Research laboratories around the world have long focused on studying the whole human genome. It is hoped that knowing the whole human genome will improve diagnostics and enable more specific therapies. Although genome analysis has not yet reached routine clinical application, whole genome sequencing has already raised many ethical and legal issues - for researchers, physicians and patients.
Which substances are suitable for treating neurodegenerative diseases such as Alzheimer's? Due to complex biochemical relationships, testing suitable drug candidates is difficult, especially in the early drug development phase. Many predictive test systems only cover individual aspects. A team from Baden-Württemberg and France is now combining different models to develop a new approach.
In cooperation with industrial partners, researchers at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart have spent many years developing innovative diagnostic tools for use in infection biology. Among these are microsystems that combine complete test procedures on a “lab-on-a-chip” (LOC) and enable simultaneous analysis of several thousand parameters relatively quickly and with little effort. The scientists hope that these systems will soon be ready for application in routine diagnostics.
The German Federal Cabinet agreed on a draft bill on human genetic testing Gene Diagnostics Law. The law protects people against the danger of potential discrimination that could result from knowledge of the genetic properties of individuals. The draft bill prohibits secret tests to determine parentage.
The benchmark paper on the Genetic Diagnostics Act which has long been heralded by the governing coalition foresees the binding counselling of people concerned. The coalition is opposed to allowing employers to require their employees to undergo genetic tests.
PCR has become a common application in medical diagnostics, in areas ranging from the detection of microbes to genetic testing. The demand for new tests is huge, given that there is a seemingly endless list of applications for which PCR can be used. dsl-Labor für Molekulargenetische Diagnostik specialises in the development of PCR tests and also gives advice and training to medical laboratory personnel. Veterinarians are among the company’s major clients since the rapid and reliable diagnosis of disease plays a particularly important role in animal husbandry.
Since January 2015, Tübingen has been home to a Centre for Personalised Medicine (ZPM). Twenty-three institutes and hospitals have joined forces to improve diagnosis of disease and develop individualised treatments for patients with a variety of diseases. In parallel, the centre also develops new diagnostic strategies. This means, for example, that data derived from the analysis of the entire genetic material of cells, proteins and metabolic processes are taken into account when stratifying patient therapy.
On the occasion of its 50th anniversary, the Institute of Human Genetics at the University Hospital of Heidelberg celebrates its major achievements in molecular genetic analyses, the diagnosis of hereditary diseases and tumour diseases as well as its research into the molecular causes of genetic defects. The largest institute of human genetics in Germany is also at the forefront of genetic counselling and debates on health policies and ethical issues.
Dr. Deborah Morris-Rosendahl and her team at the Freiburg Medical School are investigating genetic cephalic disorders which are collectively referred to as lissencephaly. The scientists offer clinical diagnostics and investigate the causes of the disease.
Sequenom, Inc. (NASDAQ: SQNM), a life sciences company providing innovative genetic analysis solutions, today announced it has partnered with LifeCodexx AG, a company focused on the development of clinically validated Next Generation Molecular Diagnostics, for the commercialization of prenatal laboratory testing services in Europe. The companies have agreed to collaborate in the development and launch of a trisomy 21 laboratory developed test and other aneuploidies testing in Germany, Austria, Switzerland, and Liechtenstein, with the potential for additional launches in other countries.
Genetic fingerprinting is a well-known technique used for paternity testing and in forensic science. However, the technique is also used in the field of agriculture. Molecular genetics makes it possible to develop and apply new research and breeding methods to the field of fruit production in order to improve production and quality standards. Dr. Haibo Xuan from the Competence Centre for Fruit Production (KOB) at Lake Constance has been working for eight years on the application of molecular genetics tools for the diagnosis of fruit diseases.
The biotech industry is the innovative driver for a pharmaceutical industry that, due to the shift from blockbluster products to personalised medicine, now depends on new concepts. The production of new drugs using genetic engineering relies on knowledge gained from genomics, proteomics and systems biology and creates new treatment strategies that combine therapy and diagnostics (i.e. companion diagnostics) to provide a specific individualised therapy.
Epigenetic mechanisms, along with gene mutations, have been shown to play important roles in the development of heart diseases. Researchers from Heidelberg have discovered that the methylation of two specific genes has an impact on the development of dilated cardiomyopathy. These epigenetic modifications have the potential to be used as molecular markers and improve the diagnosis and therapy of these particular heart diseases.
To adequately meet the growing demand for genetic diagnostics doctor scientist and bioinformatician Dr. Saskia Biskup and her husband business graduate Dr. Dirk Biskup founded the Center for Genomics and Transcriptomics or CeGAT for short in July 2009. As a supplier of DNA and RNA sequencing in the STERN BioRegion CeGAT which is based in the Technology park Tübingen Reutlingen TTR uses state-of-the-art high-throughput technologies to examine genotypes for hereditary disorders.
Being the first in Europe, the Next Generation Sequencing Laboratories of the Constance Genome and Diagnostics Centre has been accredited according to ISO 17025 from the national accreditation body for the Federal Republic of Germany (DAkks). The independent governmental institution has acknowledged the high quality standard of the sequencing service on technology platforms Illumina HiSeq and Roche GSFLX sequencing.
The company myPOLS Biotec UG, a spin-off from the University of Konstanz, specializes in services involving DNA and RNA polymerases and creates artificial enzymes by evolution in test tubes. These next-generation polymerases can be used for many research and diagnostics applications. myPOLS Biotec’s polymerases are promising enzymes for future applications with the potential to make the detection of pathogens and DNA analysis faster and easier.
mtm laboratories, a privately held diagnostics company from Heidelberg, Germany, announced the launch of CINtec® PLUS, the company’s next generation cervical cancer screening product with unmatched accuracy for the screening and management for cervical cancer. CINtec® PLUS will be launched with claims direct in Germany, Italy, Spain, France and the UK, and will also be available in other parts of the world via mtm’s nominated distributors.
A single protein can have many variants. This variability is achieved by a process known as splicing which can introduce small modifications into the mRNA transcript of a gene. Prof. Dr. Elmar Stickeler from the University Womens Hospital in Freiburg found that some of these splice variants can also induce cancer. Stickeler and his team are investigating how splicing factors change their target molecules and how this leads to breast cancer. This research is helping to increase our understanding of the molecular basis of cancer as well as potentially also leading to new strategies for the diagnosis and therapy of cancer.
“Classical treatment approaches are not the only way to ensure good health, rehabilitation and care. In fact, it is envisaged that more effective prevention will contribute to halting the development of diseases and maintaining good health. Prevention is designed to prevent health risks and diseases, make them less likely and delay their onset.” (Declaration of the German government; Official Records of Parliament 17/845, 26th February 2010)
Comprehensive genome analyses of cancer cells have shown that each tumor and cancer patient are unique and need to be treated individually. To pave the way, by 2015 the National Center for Tumor Diseases (NCT) Heidelberg aims to offer cancer patients at the NCT analyses of their individual cancer genomes to be used as the basis for personalized recommendations for treatment. This initiative from the DKFZ and NCT has been made possible by generous support from the Dietmar Hopp Foundation. The long-term goal is to facilitate the transition of research findings into applications and thus make individualized cancer treatment a part of standard clinical care. Leading technology companies including SAP, Molecular Health and GATC Biotech are collaborating in the project.
In cooperation with the company Centogene AG Prof. Dr. Michael Przybylski from the Steinbeis Transfer Center for Biopolymer Analysis and Biomolecular Mass Spectrometry at the University of Konstanz has developed a method that involves a novel substance class and enables the parallel measurement of enzyme activity based on fluorometry and mass spectroscopy. The method for which the inventors have recently filed a patent application forms the basis for the development of rapid and highly specific enzyme test systems that allow the reliable and unequivocal diagnosis of diseases. In the interview with BIOPRO Prof. Przybylski gives us some insights into his invention.
A new specialist outpatient clinic at the University Hospital of Ulm is treating haemochromatosis sufferers and is investigating the causes of this disease. Haemochromatosis which as the effect of poisoning the body is one of the most frequent hereditary diseases.
In the future, when you walk into a doctor’s surgery or hospital, you could be asked not just about your allergies and blood group, but also about your gut type. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and collaborators in the international MetaHIT consortium, have found that humans have three different gut types.
Founded by Dr. Heinz Haubruck and Prof. Dr. Bodo Liedvogel in 1998, the biotechnology company DIARECT AG (DIAgnostic by RECombinant Technology) from Freiburg sells tried and tested and new products. The company produces proteins, nucleoproteins and assay components for the diagnostics sector. These products enable the reliable identification of autoimmune disorders and infectious diseases.
Constance based GATC Biotech founds the subsidiary company LifeCodexx AG. LifeCodexx is the first web-based information service for the storage and utilisation of biological and medical data from the analysis of genetic codes and protein codes in the EU.
Tuebingen, March 7th 2014 – Today Saskia Biskup, co-founder and Managing Director of CeGaT GmbH, was announced as winner of the 2014 EU Prize for Women Innovators by the European Commission. The official celebration will take place in Brussels on Monday. The winners will receive their prizes from the President of the European Commission José Manuel Barroso at the opening ceremony of the Innovation Convention 2014, Europe’s premier innovation event. Saskia Biskup receives the prize for achieving outstanding innovations and bringing them to market.
Under its director, Prof. Dr. Peter Schirmacher, the Institute of Pathology at the University of Heidelberg has become a major liver cancer research centre, with a particular focus on hepatocellular carcinoma. The institute is looking for new diagnostic markers and new molecular targets for drugs that have the potential to be used for specifically treating this cancer.
Being diagnosed with pancreatic cancer is often a death sentence. One reason for the high mortality rate of pancreatic cancer patients is that there is currently no reliable diagnosis of early stages and no cure once the disease has reached a late stage. In an EU-funded project, 23 research groups from six countries have developed new strategies for the improved diagnosis of pancreatic cancer. Researchers at the Ulm-based Hospital for Nuclear Medicine developed molecules that enable the earlier detection of pathogenic alterations in combination with special imaging methods.
Although the biomolecule DNS has provided many explanations and hopeful projections opinions are divided over the question of DNA being the carrier of genetic information. There is a huge need for clarification. Biologists clinicians psychologists lawyers and bioethicists discussed in Tübingen.
Quick, simple and decentralized – this is how QIAGEN Lake Constance GmbH envisages diagnostics applications in the future. The Stockach-based QIAGEN subsidiary develops test systems for point-of-need diagnostics, i.e. tests that can be carried out in close proximity to the sample collection point, for example in GP surgeries. They enable the rapid identification of pathogens, and as a result the timely initiation of suitable treatment.
Preeclampsia is a hypertensive disorder of the mother during pregnancy. It is among the leading causes of death of mother and unborn child and occurs in approximately two to five percent of all pregnancies in Germany. Early detection is critical and improves the prognosis for the further course of the pregnancy.
Biomarkers are playing an increasing role in drug discovery and development. They can be used as molecular indicators for diseases and disease risks as well as for monitoring the effectiveness of therapy. Highly specific molecular biomarkers are being identified using state-of-the-art technologies from the fields of genomics, proteomics and metabolomics.
Rare diseases are conditions that are too often neglected by research, industry and medicine. Here we use Wilson’s disease as an example to illustrate the particular problems associated with research into and treatment of rare diseases and to provide information on measures that can be taken to improve the situation of people with rare diseases. These measures include central treatment and care institutions and programmes like the Wilson’s disease programme in Heidelberg, which work closely with patient organisations.
Biomarker research has moved on from proteins to nucleic acids where one of the main priorities is the use of microRNA expression profiles. The Heidelberg-based biotech company Comprehensive Biomarker Center GmbH (CBC, formerly febit) has state-of-the-art technologies and the skills and knowledge to advance the development of new nucleic acid biomarkers for complex diseases in cooperation with partners from research and industry.
Scientists have shown that a particular variant of a receptor gene impacts smoking behaviour and hence confers a 30 increase in risk of lung cancer and a 20 increase in risk of peripheral artery disease PAD.