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- Correspondence to:
Dr J D Blakey
Division of Therapeutics, Queen’s Medical Centre, University of Nottingham, Nottingham, UK; john.blakey{at}nottingham.ac.uk
MDR, a primary tool for exploratory analyses
Despite the wealth of evidence that many common diseases have a strong heritable component, genetic association studies have provided disappointingly little insight into their pathophysiology. One reason for this is that, buoyed by the success of identifying underlying variants for over 1000 uncommon conditions, researchers have largely continued to ask simple questions of more complex disorders. However, in this issue of Thorax, Park et al1 (see page 265) present an association study that uses one of a number of new statistical methods that have the potential to produce more biologically relevant associations.
A SHORT HISTORY LESSON
For much of the last century, the suggestion of a genetic association study as we now know them might have raised a few eyebrows, regardless of the leap in technology required. “Natura non facit saltum” (nature does not make leaps) was a favourite aphorism of Darwin and greatly influenced mathematical models of adaptation.2 Accepting such models, which comprise a myriad of elements, each contributing a small overall effect, implies that genetic association studies for complex disorders are fruitless in realistic population sizes. However, since the 1980s experimental evidence has accrued to challenge this notion. In a number of species, individual genetic variants have been shown to account for a large proportion of inherited trait variation,3,4 although these are markedly in the minority.5,6
STUDYING SINGLE POLYMORPHISMS
A plethora of association studies have attempted to locate these few highly influential loci for common, complex traits …
