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International GWAS confirms region on chromosome 9 linked to risk for ALS

06 September 2010

Genetic variations on chromosome 9 appear to play a role in a fatal motor neuron condition known as amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, research has found. The study by the Institute of Psychiatry at King’s College London was published in the online edition of The Lancet Neurology.

ALS is a form of motor neuron disease that is progressive, fatal and neurodegenerative. It is caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. About five to 10 per cent of ALS is hereditary. A few genes have been linked to ALS, but these explain only a small proportion of familial cases. The cause of the more common sporadic ALS remains largely unknown.

Ammar Al-Chalabi from the Institute of Psychiatry led an international team in a two-stage genome-wide association study to try and identify genetic variations responsible for increased risk of sporadic ALS. The researchers began by examining DNA samples from 599 patients with sporadic ALS and 4,144 people without the disease (‘controls’) from the UK. The results showed strong evidence of an association between two genetic variations on chromosome 9 and ALS.

To search for new genetic signals that would otherwise be difficult to detect, the researchers also did a joint analysis (the largest genome-wide association study of ALS to date), combining the UK samples with an additional 4,312 patients with ALS and 8,425 controls from seven other countries. These findings add to increasing evidence that a region of chromosome 9 is associated with increased risk of ALS across multiple populations.

Ammar Al-Chalabi comments: ‘ALS is a much feared disease, and is the commonest reason for people to seek euthanasia, so any clues that will help understand what causes it and how to find a cure are extremely valuable. This research is important in providing confirmation that a region on chromosome 9 harbours a risk gene, and also shows what can be achieved when researchers from all over the world team up. Thirteen research teams from eight different countries were involved in this project.

Chromosome 9p21.2 was the only significantly associated locus identified; this locus has also been previously linked with frontotemporal dementia. Importantly, none of the other four genetic loci that have been reported to be associated with ALS achieved significance in this analysis, suggesting that the previous associations might have been false-positive or population-specific results.

Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study can be viewed online here:

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