Genome-wide association studies taken to the next level

The Wellcome Trust Case-Control Consortium, the group responsible for a massive study of genome-wide associations (GWAS) in seven different common diseases published last year as well as a wide range of other projects in disease genetics, has just announced plans for a mind-bogglingly large expansion of their GWAS efforts.

The numbers are truly impressive: 120,000 participants, 25 different diseases, and a total cost of £30 million (nearly US$60 million). Patients and controls will be screened for up to 1 million genetic variants, as well as being subjected to analysis of genome-wide copy-number variation (insertions and deletions of DNA).

The diseases aren't all listed in the press release, but I've managed to get a breakdown from the Wellcome Trust:

Visceral leishmaniasis
Bacteraemia susceptibility
Human prion disease
Ankylosing spondylitis
Multiple sclerosis
Ulcerative colitis
Psoriasis
Coeliac disease
Asthma
Glaucoma
Schizophrenia
Psychosis endophenotypes
Parkinson’s disease
Partial epilepsies
Ischaemic stroke
Abdominal aortic aneurysms
Myocardial infarcation
Coronary artery disease
Extreme and early onset obesity
Response to statin treatment
Barrett’s oesophagus and oesophageal adenocarcinoma
Breast Cancer
Adult glioma
Pre-eclampsia
Endometriosis

There's something in that for nearly everyone, as well as an interesting addition that isn't a disease at all: reading and mathematics abilities in 12-year-old children enrolled in the UK Twins Early Development Study. This marks an interesting (and potentially extremely controversial) foray into the world of cognitive genetics. Watch this space - the media coverage of this aspect of the project is unlikely to be universally positive.

I haven't yet been able to find out the sample sizes for each disease, but it's clear from the total number quoted in the press release that at least some of these cohorts will be quite well-powered - assuming they use a large, shared group of controls, the average sample size is likely to be more than 4,000 patients.

I've recently spent quite a bit of my time talking down the power of genome-wide association studies. Nonetheless, a study of this magnitude - combining SNP data with copy number variation - is likely to capture a sizeable (albeit by no means complete) chunk of the genetic risk variants for many of these diseases. Having comparable data-sets from so many different diseases will also facilitate the identification of common variants that influence risk for multiple diseases, as has already been demonstrated for IL23R in several auto-immune conditions.

In addition, the WTCCC and its partners are assembling an enviable collection of well-characterised DNA samples from patients and controls that can be rapidly deployed for large-scale sequencing approaches once the cost of sequencing drops far enough.

Exciting times...


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