Assembling the conditions for Genome Wide Association Studies: The story of the Wellcome Trust Case Control Consortium

Speaker: Dr. Catherine Heeney # University of Edinburgh

22nd Jan 2018

15:30 - 17:00

6th Floor Staff Room, Chrystal Macmillan Building

2007 has been termed the ‘year of the GWAS’ because several prominent papers from different scientific groups published the results from Genome Wide Association Studies (GWAS) that year. Following the huge resources invested in the Human Genome Project there was a recognition of the methodological barriers to understanding the role of genetic variants and fulfilling the promises for common complex disease (WT 1999). One method, the Genome Wide Association Study (GWAS) was eventually positioned as a solution to these problems. Despite being a methodological success in detecting genes involved in prevalent diseases such as Type 1 and 2 diabetes, it was rapidly acknowledged that converting GWAS findings into health interventions would be challenging (Maniolo et al 2009). Some of the problems with GWAS were arguably present from the outset for common complex disease genetics. It was widely acknowledged, for example, that one reason that the genes involved in causing common complex disease were difficult to determine was taken individually their causal effect was small. Nevertheless, the widespread uptake of GWAS to search for implicated genes is evident from a series of diagrams available on the website of the European Bioinformatics Institute, which show a year on year increase in associations from GWA studies 2007 - 2013 (EBI 2014). Using a theoretical framing offered by the philosophy of Deleuze I will address the question of how GWAS become such a key focus for those interested in finding the genetic causes of common complex disease? This question will be considered here in relation to one particular example, carried out by the Wellcome Trust Case Control Consortium (WTCCC) between 2005 and 2007. This GWAS was one of the first hypothesis free (without pre-specified candidate genes), large scale (comprising thousands of cases and controls) association study carried out in the UK and among the first in the world. The paper from the project, entitled ‘Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls,’ appeared in Nature in 2007 and has more than 4000 citations to date. I draw on interview material from 18 interviews with members of WTCCC, and upon a review of scientific literature relating to the genetics of common complex disease, in the 80s, 90s and early 2000s and documents pertaining to the WTCCC bid and the project provided by interviewees. Employing a Deleuzian framing I will argue that GWAS emerged from an assemblage, which was created in response to a series of methodological problems associated with the small size of genetic effects for common complex disease.