Wellcome Trust Case Control Consortium

The Wellcome Trust Case Control Consortium (WTCCC) is one of the largest collaborative studies ever undertaken to look at genetic variation in the human population and the role this plays in disease susceptibility. The Wellcome Trust Sanger Institute was a major lead in the inception and development of this project in 2005, which received almost £9 million in funding at the time from the Wellcome Trust and incorporates 50 top UK research groups. The project exploits the latest computational scan technologies for genome-wide association (GWA) studies applied to diseases such as breast cancer, type 1 diabetes and cardiovascular disease among others.

The SNP data generated by microarray experiments in the US are sent to be analysed at the Wellcome Trust Sanger Institute. WTCCC1 is ongoing, studying 16,000 individuals with disease phenotypes and 3000 case controls, and further experiments into copy-number variation are being carried out on these samples.

Following from the success of this project, the Wellcome Trust Sanger Institute proposed and planned a second wave of GWA studies - the WTCCC2 project - which is funded by the Wellcome Trust to analyse a further 120,000 samples and 13 more conditions including multiple sclerosis, pre-eclampsia and Parkinsons disease. The WTCCC+ project leads on from the copy-number variation studies of WTCCC1 to confirm not only the variants but also the actual number of copies at a given locus. WTCCC3 is an additional wave of GWA studies launched in 2009 and funded by the Wellcome Trust to analyse five complex traits: anorexia nervosa, renal-transplant dysfunction, primary biliary cirrhosis, tuberculosis, pre-eclampsia and HIV host control.

Peer-reviewed publications are issuing thick and fast from these genetic analyses and are proving to have wide-ranging implications for research into human diseases. The most recent publication contributed to evidence in support of diagnostic considerations in schizophrenia and mood-psychosis disorders1. Another reported the analysis of variants in loci associated with serum uric acid levels, which play a role in gout and in cardiovascular disorders2. A third reported the discovery of a novel type-1 diabetes locus3.

This is an exciting time for the study of human genetic variation with results being generated at a rapid pace, and the WTCCC projects are at the heart of the discovery of the multi-gene factors that contribute to complex but common human diseases.

Wellcome Trust Case Control Consortium website.

References

  • Association of RASGRP1 with type 1 diabetes is revealed by combined follow-up of two genome-wide studies.

    Qu HQ, Grant SF, Bradfield JP, Kim C, Frackelton E, Hakonarson H and Polychronakos C

    Journal of medical genetics 2009;46;8;553-4

  • Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept.

    Hamshere ML, Green EK, Jones IR, Jones L, Moskvina V, Kirov G, Grozeva D, Nikolov I, Vukcevic D, Caesar S, Gordon-Smith K, Fraser C, Russell E, Breen G, St Clair D, Collier DA, Young AH, Ferrier IN, Farmer A, McGuffin P, Wellcome Trust Case Control Consortium, Holmans PA, Owen MJ, O'Donovan MC and Craddock N

    The British journal of psychiatry : the journal of mental science 2009;195;1;23-9

  • Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations.

    Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, Mangino M, Albrecht E, Wallace C, Farrall M, Johansson A, Nyholt DR, Aulchenko Y, Beckmann JS, Bergmann S, Bochud M, Brown M, Campbell H, EUROSPAN Consortium, Connell J, Dominiczak A, Homuth G, Lamina C, McCarthy MI, ENGAGE Consortium, Meitinger T, Mooser V, Munroe P, Nauck M, Peden J, Prokisch H, Salo P, Salomaa V, Samani NJ, Schlessinger D, Uda M, Völker U, Waeber G, Waterworth D, Wang-Sattler R, Wright AF, Adamski J, Whitfield JB, Gyllensten U, Wilson JF, Rudan I, Pramstaller P, Watkins H, PROCARDIS Consortium, Doering A, Wichmann HE, KORA Study, Spector TD, Peltonen L, Völzke H, Nagaraja R, Vollenweider P, Caulfield M, WTCCC, Illig T and Gieger C

    PLoS genetics 2009;5;6;e1000504

* quick link - http://q.sanger.ac.uk/kd78lx1b