CRP HuGE Consortium 
Principal OrganisersProfessor George Davey Smith and Nic Timpson. DescriptionThe Network was initially proposed by Prof G Davey Smith at a meeting held at the Department of Social Medicine, Bristol University. Dr Aroon Hingorani, Dr Manj Sandhu, Dr Liam Smeeth, Dr Debbie Lawlor, Mr Nic Timpson and Dr Juan Casas were present at this meeting representing the University College London, Cambridge University, the University of Bristol and the London School of Hygiene and Tropical Medicine respectively. The gathering of this group and the proposal of a network formation between those present (and a potentially wider group), was conceived in recognition of joint interests in the role of C-reactive protein and CRP genetics in common disease and in light of the positive nature of previous collaborations. This grouping was also prompted by a common recognition of a requirement of the pooling of available resources in efforts to enhance the statistical robustness of current analytical approaches. Our common interest in the role of CRP and related pathways allows selection criteria for potential projects to be relatively stringent and as such would include biomarkers, genetic variants and molecules which are directly involved in the expression, regulation and modulation of this protein and its downstream effects. Furthermore, this approach prompts the application of analytical techniques exploiting the nature of genetic variation in and relating to the CRP gene and serum CRP concentrations. For example, the application of Mendelian randomization as a technique employing relevant genetic variation in the assessment of causal influences of CRP previously assessed by traditionally observational methods, will be encouraged. This gene-based consortium therefore aims to provide the appropriate level of resolution, yet flexibility in the assessment of inflammatory pathways and in particular the role of CRP in common disorders. This network has also since had the fortunate opportunity of including the valuable insights of the Max Planck Institute of Evolutionary Anthropology, as mediated through Professor Mark Stoneking and colleagues. Whilst principally a section of the network aimed for further development of an evolutionary genetics/epidemiology arm, this currently offers an invaluable resource with respect to the assessment of inter-population variability, the access and use of whole genome resources and evidence for selective pressures acting on target variation. This Network is currently embryonic and as such has not initiated collaborative work. The current focus of this group is to unite research initiatives which may be brought together to offer sound research opportunities. As it stands, this network offers a forum for groups and cohorts which have resources available and suited for addressing CRP/inflammation/common disease orientated research questions. As this network both expands and begins to operate, collaborating resource bases and their output will be posted. The CRP-Coronary Disease Genetics Collaboration is a consortium of investigators generating and pooling data on a total of about 20 000 coronary disease cases and about 20 000 controls on the association between CRP polymorphisms and coronary risk to help evaluate the likelihood of any causal association between circulating CRP concentrations and coronary heart disease. The coordinating centre for this initiative is jointly based at the University of Cambridge, University College London and the London School of Hygiene and Tropical Medicine, with collaborators based in several centres in the UK (including Bristol and Oxford), other Western European countries, and North America. For more information, please contact John Danesh (john.danesh@phpc.cam.ac.uk) or Aroon Hingorani (a.Hingorani@ucl.ac.uk). Further details of this and other work that develops as this network both expands and begins to operate, will be posted on the website when they become available. Direct Participating MembersUniversity of Bristol – Department of Social Medicine
University College London
London School of Hygiene and Tropical Medicine
Cambridge University
Oxford University
King’s College London/St George’s Medical School
University of Western Australia (UWA)
University of Newcastle
Norwegian University of Science and Technology
GSF – Institute of Epidemiology
The Max Planck Institute for Evolutionary Anthropology - Leipzig
Resource TablesAvailable on request. News and Research DevelopmentsTo be updated regularly with respect to the development of specific aspects of research within this group. Studies Included
Web Links
References1. Timpson NJ, Lawlor DA, Harbord R, et al. C-reactive protein and metabolic syndrome: Mendelian randomisation suggests associations are non-causal. Lancet 2005;366:1954-1959. 2. Lawlor DA, Davey Smith G, Rumley A, Lowe GD, Ebrahim S. Association of fibrinogen and C-reactive protein with prevalent and incident coronary heart disease attenuated by adjustment for confounding factors: British Women's Heart and HEalth Study. Thrombosis and Haemostasis 2005;93:955-963. 3. Davey Smith G, Lawlor DA, Harbord R, et al. Association of C-reactive protein with blood pressure and hypertension: lifecourse confounding and Mendelian randomisation tests of causality. Arteriosclerosis, Thrombosis & Vascular Biology 2005;25:1051-1056. 4. Davey Smith G, Harbord R, Ebrahim S. Fibrinogen, C-reactive protein and coronary heart disease: does Mendelian randomization suggest the associations are non-causal? Qjm 2004;97(3):163-6. 5. Davey Smith G, Ebrahim S. What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? British Medical Journal 2005;330:1076-1079. 6. Davey Smith G, Ebrahim S. Mendelian Randomisation: prospects, pitfalls and limitations. International Jounal of Epidemiology 2004;33:30-42. 7. Davey Smith G, Ebrahim S. 'Mendelian Randomisation': can genetic epidemiology contribute to understanding environmental determinants of disease? International Jounal of Epidemiology 2003;32:1-22. 8. Ioannidis JPA, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nature Genetics 2006;38:3-5. 9. Hingorani A, Humphries S. Nature's randomised trials. Lancet 2005;366(9501):1906-8. 10. Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.[see comment]. New England Journal of Medicine. 2004;350:1387-97. 11. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore JR, Pepys MB. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.[see comment]. Bmj. 2000;321:199-204. |