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A Genome Wide Association Study in Ischaemic Stroke

Hugh Markus

Peter Rothwell, Martin Farrall, Cathie Sudlow, Martin Dichgans, Pankaj Sharma, Stephen Bevan.

Stroke is one of the most important health problems in the UK. It is the third major cause of death and is the major cause of neurological disability in the UK and other similar countries. It is becoming an increasing problem as it is much more frequent in the elderly and this proportion of the population is increasing. Although there are some effective preventative therapies, we cannot prevent or treat many stroke cases. Considerable evidence suggests genetic factors are important. By identifying genetic factors we may identify new stroke mechanisms which will allow us to formulate completely novel treatment strategies. Even if these have only a modest effect on risk, this would have a very major population benefit due to the high prevalence and large cost (to both patients, carers and the health economy) of stroke.

Stroke remains the 3rd leading cause of death and leading cause of disability in the developed world. Accumulated evidence suggests a strong familial contribution to stroke susceptibility. Identifying genetic risk factors for stroke may offer novel biological insights that are crucially needed for advancing preventative therapeutics. An initial genome-wide screen will be performed on 4189 stroke cases, which will be compared with an equal number of already genotyped controls from the WTCCC and the German KORA-gen resource. Replication will be performed in approximately 4432 cases from 2 further UK and 2 European populations (using already genotyped controls from TwinsUK study for the UK cases, and already collected controls for the continental European cases), with final replication in 2873 cases and 2743 controls from 4 US populations.