Professor Hugh Watkins

hugh watkins

The CureHeart Project is led by Hugh Watkins, Professor of Medicine at the University of Oxford.  Professor Watkins heads the Radcliffe Department of Medicine, University of Oxford and is the Director of the BHF Centre of Research Excellence at Oxford. 

I am a clinician scientist, focussing on the genetic basis of inherited heart disease. I have made a series of contributions to the understanding of the genetic basis of inherited cardiac diseases, and have used these advances to pioneer new approaches to diagnosis and therapy with substantial impact on human health. I have built one of the UK’s leading clinical programmes in Inherited Cardiac Conditions and driven the adoption of genetic testing as the standard of care; the Oxford lab has probably the largest single centre experience in genetic testing in cardiomyopathy worldwide. 

Throughout my career, I have placed particular emphasis on research leadership and training of others. I have been head of department for over 25 years and now head a large multidisciplinary department of medicine with research interests that span the translational spectrum. I have overseen growth in cardiovascular research that has made Oxford an internationally leading institution in the field; this has included Directorship, for 20 years, of competitively awarded capacity building programmes funded by the Wellcome Trust and the BHF.  I have extensive experience of leading multinational collaborative research programmes supported by international funders.

I have published over 400 papers, my h-index is 113, and I was a Web of Science highly cited researcher 2017, 2018. I am a Fellow of the Academy of Medical Sciences and a Fellow of the Royal Society (FRS).

Find out more about Professor Watkins' work. 

CureHeart - information for patients and families



Adoption of genetic testing in cardiomyopathy

My group generated the data needed for regulatory approval and NHS commissioning of genetic testing in Inherited Cardiac Conditions in the UK, including evidence of technical feasibility, clinical utility for identifying individuals at risk, and health economic assessment.  These data supported award of a Class I indication in European guidelines in 2014.

Genetic testing is now considered the first line approach for managing families affected by inherited cardiomyopathies, and this has changed practice worldwide. I have had a leading role in promoting adoption of cascade screening for the identification of mutation carriers. More recently, my group has built on its experience in genetic testing in cardiomyopathy (now including over 14,000 families), and the availability of population scale data on rare variants, to demonstrate that many of the more recently proposed disease genes are not reliably associated with disease. This has again changed practice in cardiomyopathy testing and, as the first reanalysis of Mendelian gene pathogenicity using this quantitative appraoch, it has triggered widespread reanalysis across cardiac diseases and beyond.

  • Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H. (2017). Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 19:192-203. doi: 10.1038/gim.2016.90.  

Molecular genetic basis of cardiomyopathy

Working in the Seidman laboratory, I was integrally involved in the discovery of the major disease genes for hypertrophic cardiomyopathy, the most common and clinically important Mendelian cardiac disorder, which provided a paradigm for the field. The same genes were later shown to also be major causes of dilated cardiomyopathy. Additional cardiomyopathy disease gene discoveries followed from my laboratory and, more recently, definition and disease gene identification for two novel inherited arrhythmia syndromes.

  • Watkins H, Rosenzweig A, Hwang D-S, Levi T, McKenna WJ, Seidman CE, Seidman JG.  (1992). Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy.  N Engl J Med  326:1108-1114. doi: 10.1056/NEJM199204233261703.
  • Watkins H, McKenna WJ, Thierfelder L, Suk HS, Anan R, Spirito P, Matsumori A, Moravec C, Seidman JG, Seidman CE.  (1995). Mutations in the genes for cardiac troponin T and α-tropomyosin in hypertrophic cardiomyopathy.  N Engl J Med 332:1058-1064. doi: 10.1056/NEJM199504203321603.
  • Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE.  (1995). Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy.  Nature Genetics 11:434-437. doi: 10.1038/ng1295-434.

Cardiomyopathy disease mechanisms and human phenotypes

In functional studies, my group demonstrated that the mutant myofilament proteins in hypertrophic cardiomyopathy increase calcium-sensitivity and the energy cost of force production, and that dilated cardiomyopathy mutations have opposite effects. Together with new genetic data, these findings highlighted novel aspects of muscle physiology and the importance of energetic compromise in cardiomyopathy. I have built a leading collaboration using cardiac magnetic resonance imaging and spectroscopy to enable tissue characterisation in vivo in patients with cardiomyopathy (including measurements of energetic homeostasis, oxygenation, fibrosis and fibre disarray).

  • Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H.  (2001). Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.  Hum Mol Genet. 10:1215-20. doi: 10.1093/hmg/10.11.1215.
  • Mirza M, Marston S, Willott R, Ashley C, Mogensen J, McKenna W, Robinson P, Redwood C, Watkins H. (2005). Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype. J Biol Chem. 280(31):28498-506. doi: 10.1074/jbc.M412281200
  • Ariga R, Tunnicliffe EM, Manohar SG, Mahmod M, Raman B, Piechnik SK, Francis JM, Robson MD, Neubauer S, Watkins H. (2019). Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias. J Am Coll Cardiol. 73:2493-2502. doi: 10.1016/j.jacc.2019.02.065.

Defining the contribution of common genetic variants in both common and rare disease

For over 20 years, my group has built the patient cohorts and infrastructure necessary for large scale genome-wide association analysis for detection of common susceptibility variants. Focusing first on coronary artery disease, I have had a leading role in in the consortia (PROCARDIS and C4D, which I led, and thereafter Cardiogram+C4D, where I have been a member of the executive) which have defined almost all of the coronary disease loci now used for polygenic risk score for disease prediction and for derivation of new, genetically validated, therapeutic targets. This included genetic evidence that lipoprotein Lp(a) is causally related to coronary disease, and hence a valid drug target; novel specific Lp(a) lowering agents are now the focus of multiple pharmaceutical companies. More recently, we have shown the surprisingly large common variant contribution to risk of developing hypertrophic cardiomyopathy, with important implications for cascade screening, individualized risk prediction and management of comorbidities.

  • Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, Bennett D, Silveira A, Malarstig A, Green FR, Lathrop M, Gigante B, Leander K, de Faire U, Seedorf U, Hamsten A, Collins R, Watkins H, Farrall M. (2009). Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 361(26):2518-28.  [Watkins and Farrall corresponding authors.] doi: 10.1056/NEJMoa0902604.
  • Nelson, C. P., Goel, A., Butterworth, A. S., Kanoni, S., Webb, T. R., Marouli, E., . . . Watkins H, Deloukas, P. (2017). Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nature Genetics 49, 1385-1391. (Watkins corresponding author). doi: 10.1038/ng.3913.
  • Harper AR, Goel A, Grace C, Thomson K, Petersen SE, Xu X, Waring A, Ormondroyd E, Kramer C, Neubauer S, Tadros R, Wars JS, Bezzina C, Farrall M, Watkins H. (2021). Common genetic variants, and modifiable risk factors, underpin susceptibility and expressivity in hypertrophic cardiomyopathy. Nature Genetics 2021;53:135-142. doi: 10.1038/s41588-020-00764-0.