Wellcome Trust Case Control Consortium

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WTCCC1

The Wellcome Trust Case Control Consortium (WTCCC) is a group of 50 research groups across the UK which was established in 2005. The WTCCC aims were to exploit progress in understanding of patterns of human genome sequence variation along with advances in high-throughput genotyping technologies, and to explore the utility, design and analyses of genome-wide association (GWA) studies. The WTCCC has substantially increased the number of genes known to play a role in the development of some of our most common diseases and has to date identified approximately 90 new variants across all of the diseases analysed. As well as confirming many of the known associations, some 28 in total, the WTCCC has also identified many novel variants that affect susceptibility to disease.

The WTCCC aims to complete the initial survey of common variation for association to disease, and to examine the replicated association signals detected through resequencing and fine-mapping. The WTCCC will also carry out a major experiment to address the genome-wide measurement of copy number variation (CNV) within the 19,000 samples tested in phase one (16,000 disease samples and 3,000 common controls) and additional samples from breast cancer. Further information

WTCCC2

In recognition of the success of the WTCCC and to capitalise on the success of the GWA approach, a further round of GWA studies were funded in April 2008. These include 15 WTCCC-collaborative studies and 12 independent studies be supported totalling approximately 120,000 samples. Many of the studies represent major international collaborative networks that have together assembled large sample collections.

WTCCC2 will perform genome-wide association studies in 13 disease conditions: Ankylosing spondylitis, Barrett's oesophagus and oesophageal adenocarcinoma, glaucoma, ischaemic stroke, multiple sclerosis, pre-eclampsia, Parkinson's disease, psychosis endophenotypes, psoriasis, schizophrenia, ulcerative colitis and visceral leishmaniasis. WTCCC2 will also investigate the genetics of reading and mathematics abilities in children and the pharmacogenomics of statin response. Over 60,000 samples will be analysed using either the Affymetrix v6.0 chip or the Illumina 660K chip. The WTCCC2 will also genotype 3,000 controls each from the 1958 British Birth cohort and the UK Blood Service control group, and the 6,000 controls will be genotyped on both the Affymetrix v6.0 and Illumina 1.2M chips.

WTCCC3

To build further on the success of the GWAS approach demonstrated by the WTCCC, the Wellcome Trust has provided support for a further round of GWA studies in January 2009. These include 5 WTCCC-collaborative studies to be carried out in WTCCC3 and 5 independent studies, across a range of diseases. Many of the studies represent major international collaborative networks that have together assembled large sample collections.

WTCCC3 will perform genome-wide association studies in the following 4 disease conditions: primary biliary cirrhosis, anorexia nervosa, pre-eclampsia in UK subjects, and the interactions between donor and recipient DNA related to early and late renal transplant dysfunction. The WTCCC3 will also carry out a pilot in a study of the genetics of host control of HIV-1 infection. Over 40,000 samples will be analysed using the Illumina 660K chip. The WTCCC3 will utilise the 6,000 control genotypes generated by the WTCCC2.

Data release

Genotype data from WTCCC1 is available by application to the Consortium Data Access Committee (cdac@wellcome.ac.uk). To support the studies within WTCCC and also the independent studies, the WTCCC will first genotype 6,000 common controls; 3,000 from the 1958 British Birth Cohort and 3,000 from the UK Blood Service Collection, and the data will be made available immediately through the existing controlled data access mechanism of the WTCCC. Data generated from the disease samples in WTCCC2 will be made available six months after data generation and QC, or upon publication.