Translational Genomics Study Group

TBC

Lead
Aroon Hingorani, UCL Professor of Genetic Epidemiology

Members
Professor John Overington, Honorary Chair (Medicines Discovery Catapult)
Chris Finan, Senior Research Associate (Provost’s Excellence Fellow)
Floriaan Schmidt, Honorary Senior Lecturer (University of Groningen)
Tina Shah, Research Associate
Sandesh Chopade, Research Assistant
Jorgen Engmann, Data Scientist
Vicky Garfield, Research Associate (joint with MRC LHA)
Valerie Kuan, PhD student (Wellcome Clinical Training Fellowship)
Costas Parisinos, PhD student (Wellcome Clinical Training Fellowship; joint with Institute of Health Informatics)
Magda Zwierzyna, PhD student (joint with Benevolent AI)
Roshni Joshi, PhD Student (BHF 4-year PhD scheme)
Maria Gordillo-Maranon, PhD Student (BHF 4-year PhD scheme)

Alumni
Professor Meena Kumari (University of Essex)
Professor Juan Pablo Casas (UCL Institute of Health Informatics)
Dr Reecha Sofat (UCL Institute of Health Informatics)
Dr Michael Holmes (University of Oxford)
Dr Dan Swerdlow (Genomics PLC and UCL Institute of Cardiovascular Science)
Dr Sonia Shah (University of Brisbane)
Dr Claudia Giambartolomei (UCLA)
Dr Lila Mayahi (St.George’s University of London)
Dr Karoline Kuchenbaecker (UCL Institute of Psychiatry and UCL Genetics Institute)
Dr Felix Kruger (Benevolent AI)

Location
UCL Farr Institute, 222 Euston Road, NW1 2DA

Funding
British Heart Foundation, Wellcome Trust, National Institute of Health Research, UCL NIHR Biomedical Research Centre, Rosetrees Trust and Stoneygate Trust

Overview
Human disease arises from genetically-encoded or acquired perturbations in protein expression or activity. These initiate the transition from wellbeing to illness through effects on physiology, metabolism and organ and systems function. Therefore, understanding disease mechanism centres on the identification of the relevant protein-disease relationships and the downstream phenotypic consequences. Knowledge of these is a pre-requisite for drug development (since almost all drug targets are proteins), and also for precision medicine since the prevailing mechanisms in an individual, by definition, deviate from average effects in populations. New opportunities for deeper understanding of human disease mechanisms and individual differences in susceptibility come from the falling cost, accuracy and scalability of genomic (and now proteomic and metabolomic) technologies; safe, high-resolution, imaging modalities such as magnetic resonance imaging; as well as the availability for research, of millions of routine clinical measurements and health outcomes in NHS electronic health records. With these tools, connectivity between the genome, environment and phenome (in individuals and in populations) becomes possible with unprecedented scale and detail.

Our work centres of discovering genotype-phenotype relationships through multi -omics and disease outcome data from population and patient cohorts. We use statistical genetics, bioinformatics and computational biology methods, to organise, make sense of and apply the data to support precision medicine. A particular focus is on accurate drug target identification and validation through human genomics.

The group serves as the co-ordinating centre for the University College London-Edinburgh-Bristol Consortium of cohort studies.

Highlights

  • Finan C*, Gaulton A*, Kruger FA, Lumbers RT, Shah T, Engmann J, Kelley R, Karlsson A, Santos R, Overington JP*, Hingorani AD*, Casas JP*. The druggable genome and support for target identification and validation in drug development. Science Translational Medicine 2017; 29 Mar 2017 DOI: 10.1126/scitransmed.aag1166
  • Daniel I Swerdlow*, David Preiss*, Karoline B Kuchenbaecker, …., Aroon D Hingorani†, Naveed Sattar†.  HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 2014 Published Online September 24, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)61183-1. †Joint senior authors.
  • Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium, Hingorani AD, Casas JP. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012 Mar 31;379(9822):1214-24. Epub 2012 Mar 14. PMID: 22421340
  • C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC), Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T, Engert JC, Clarke R, Davey-Smith G, Nordestgaard BG, Saleheen D, Samani NJ, Sandhu M, Anand  S, Pepys MB, Smeeth L, Whittaker J, Casas JP, Thompson SG, Hingorani AD*, Danesh J*. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ. 2011 Feb 15;342:d548. doi: 10.1136/bmj.d548. PubMed PMID: 21325005; PubMed Central PMCID:  PMC3039696. *Joint senior authors
  • Hingorani A, Humphries S. Nature’s randomised trials. Lancet 2005; 366; 1906-8