Can it happen again? Informing pregnancy decisions using personalised risk information

When a child is diagnosed with a serious genetic condition caused by a new genetic change (de novo mutation), parents often worry about the chances of this happening again in future pregnancies. Currently, the general recurrence risk given in clinic is a population average (usually ~1-2%). However, there is now a new strategy, called PREGCARE, that can refine this risk for each individual couple. This presentation by Professor Anne Goriely and Dr Alison Kay from the University of Oxford explores how it works, its potential benefits and what it means from a practitioner’s perspective. Dr Emilie Wigdor introduces the session.

Hear from Professor Lindgren about how Oxford researchers at the BDI are developing, evaluating and deploying efficient methods for acquiring and analysing information for large clinical research studies to identify the associations between lifestyle exposures, genetic variants, infections and health outcomes around the globe. Cecilia Lindgren has a PhD in Molecular Genetics with a specialisation in endocrinology from the University of Lund, completed in sponsorship by the Witehead Institute at MIT, Cambridge, USA. She was a postdoctoral fellow at the University of Lund and at the Karolinska Institutet, and a Scholar in Residence at the Broad Institute in Cambridge, USA, before joining the University of Oxford. She is a Wellcome Trust Investigator and co-founder/co-chair of the International Common Disease Alliance. She has been a Senior Research Fellow at St Anne’s since 2016, when she joined the steering group of the Centre for Personalised Medicine (at St Anne’s).

Holly Eggington is a DPhil student in Cancer Science, studying interaction between cellular compartments in colorectal cancer at the Wellcome Centre for Human Genetics. She is also a medical student, passionate about bridging the boundary between laboratory and clinical research, as well as being President of the Oxford University Personalised Medicine (OUPM) Society.

Christopher Gyngell is a Team Leader in Biomedical Ethics at the Murdoch Children’s Research Institute; Senior Lecturer in the Department of Paediatrics at the University of Melbourne; and a Senior Research Fellow at the Melbourne Law School. His research interests lie primarily in the ethical implications of biotechnologies and the philosophy of health and disease Danya Vears is a social scientist with a genetic counselling background who explores ethical issues relating to genetic testing. She is a Senior Research Fellow and Team Leader at the Biomedical Ethics Research Group, Murdoch Children’s Research Institute, and holds honorary positions at University of Melbourne, and as a Guest Professor at the Centre for Biomedical Ethics and Law, KU Leuven. Danya’s current research focuses on the practical, social and ethical issues relating to the use of next generation sequencing technologies in both clinical and research settings. Danya is a member of the Education, Ethics and Social Issues Committee of the Human Genetic Society of Australasia and also the Global Alliance for Genomics and Health.

Tim Elliott left the University of Oxford (Balliol) with a first in Biochemistry in 1983 and completed his PhD in cancer immunotherapy at the University of Southampton in 1986. He did his postdoctoral training at the Massachusetts Institute of Technology with Herman Eisen at the Center for Cancer Research. In 1990 he returned to the University of Oxford to join the Institute for Molecular Medicine as a Wellcome Trust Research Fellow, joining a key group of immunologists studying antigen presentation at the molecular level. In 1993 he was appointed to a lectureship and later a Professorship at Balliol College, University of Oxford, as a Wellcome Trust Senior Fellow in Basic Biomedical Science. In 2000, he moved to the University of Southampton as Professor of Experimental Oncology and five years later became Associate Dean for the Faculty of Medicine. In 2015 he stepped down from this role to take up interim Pro Vice Chancellor (Research) for the University of Southampton. He was the Founding Director of the new Southampton Centre for Cancer Immunology which opened in 2018, and Deputy Director of the interdisciplinary Southampton Institute for Life Sciences for which he is now an external consultant. He is a world leader in the field of antigen presentation and T cell biology and has incorporated discoveries in the areas of antigen processing, T cell regulation and immunodominance into the development of new cancer immunotherapies and is the recipient of a Royal Society/Wolfson Research Merit Award. He is a Fellow of the Royal Society for Biology and Fellow of the Academy of Medical Sciences; founding Editor-in-Chief of the journal Immunotherapy Advances published by the British Society for Immunology; and chairs the Cancer Research UK Cancer Immunology expert review committee. Professor Elliott was appointed to the Kidani Chair of Immuno-Oncology at the University of Oxford in 2020.

Talk from Dr Patrick Short, CEO of Sano Genetics, ‘Accelerating precision medicine research with digital and at-home testing’. Recorded on Thursday 15th December.

We were delighted to host Dr Shiri Shkedi-Rafid on Tuesday 24th January 2023 at the Wellcome Centre for Human Genetics for her talk, Challenges of genomic testing in gamete-donated pregnancies. Dr Shkedi-Rafid is a senior genetic counsellor at Hadassah Medical Center, with over 15 years of clinical experience both in Israel and the UK.

We were delighted that Dr Maya Sabatello, Assistant Professor of Clinical Bioethics at Columbia University, gave her talk, ‘Ableism and (dis)trust: Disability Ethics and Inclusion in Precision Medicine Research.’ Recorded on Tuesday 21st February 2023 at St Anne’s College, Oxford.

In this interview, CPM Director Professor Anneke Lucassen speaks to Professor Sir Walter Bodmer, asking him to reflect on his career and to think about next steps in the field of personalised medicine. Professor Bodmer is a geneticist with a wide field of study. He has made major contributions to the study of the genetics of human populations, gene mapping and cancer genetics and to our understanding of the human tissue typing system. Early in his career, he helped to discover the human leukocyte antigen (HLA) system, vital for the success of organ and bone marrow transplants. Walter’s interest in human populations led him to set up a UK population gene bank that could be used as a control group in research. More recently, he has successfully grown bowel cancer cells in the lab in structures similar to those found naturally inside the bowel. Professor Bodmer is credited with beginning the movement for the public understanding of science, having chaired the first committee set up to establish standards for communicating science and technology. He was the first Director General of the Imperial Cancer Research Fund and was knighted in 1986. [Biography adapted from https://royalsociety.org/people/walter-bodmer-11105/]

Summary: Despite decades of research, it is still not clear what causes Alzheimer’s disease. Most research into dementia risk factors is observational and suffers from the pervasive issues of confounding and reverse causation. Survival bias is also problematic when studying very late life diseases and can lead to spuriously protective associations between factors that increase risk of premature mortality (e.g. smoking) and dementia risk. Mendelian randomization has started to shed some light on which risk factors are likely to be causal, and therefore which interventions may reduce dementia burden. It has also provided clues to the ages at which interventions are likely to be successful. Emma will provide an overview of the research into dementia risk factors, discuss where the research is heading, and which interventions look the most promising. Bio: Dr Emma Anderson is Associate Professor of Epidemiology at the Division of Psychiatry, UCL. Emma’s work to-date has focussed on the application of novel causal inference methodology, such as Mendelian randomization, polygenic risk score analysis and offspring instrumental variable analysis, to identify modifiable causal risk factors for Alzheimer’s disease. Emma’s UKRI Future Leaders Fellowship will extend this work by identifying genetic and environmental determinants of vascular dementia. This talk was held on Zoom on 28 November 2023 and it was chaired by Dr Padraig Dixon, Junior Research Fellow at the Centre for Personalised Medicine and a Senior Researcher in Health Economics in the Nuffield Department of Primary Care Health Sciences at Oxford.