Studies confirm region of chromosome 9 linked to risk for amyotrophic lateral sclerosis

Aug 30, 2010

Genetic variations on chromosome 9 have been identified that might have a role in the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Findings in two separate Articles published Online First in The Lancet Neurology add to the evidence that a region of chromosome 9 is linked to a higher risk of ALS across multiple populations.

About 5-10% of ALS (also known as motor neuron disease or Lou Gehrig's disease) 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. Several recent genome-wide association studies (GWAS) have identified a number of possible susceptibility genes, but replication of these associations has not been successful in independent studies. In 2006, linkage between familial ALS and chromosome 9 was first identified in Scandinavian families. However, subsequent research has not revealed a disease-causing .

In the first Article, Bryan Traynor from the National Institutes of Health, USA, and international colleagues did a GWAS to identify genetic risk factors for ALS in the Finnish population.

318 167 DNA variations known as single (SNPs) were analysed in the genome of each of the 405 patients with ALS (93 familial and 312 sporadic) and 497 controls.

The researchers found two genetic variations that contribute to risk of ALS. One was identified in the SOD1 gene, which has previously been associated with risk of ALS, on chromosome 21q (rs13048019), and the other was on chromosome 9p (rs3849942). One or other of these variations was found in more than 70% of patients with a family history of ALS, thus explaining a substantial proportion of familial ALS in Finland.

Additionally, the investigators defined a group of 42 SNPs (a 42-SNP haplotype) on chromosome 9p (shared by 44% of patients with familial ALS and 19% with sporadic ALS) that was linked to a significantly increased risk of ALS in the Finnish population. The shared haplotype also suggests a possible founder effect for the chromosome 9p locus in Finland.

The authors conclude: "The chromosome 9p21 locus is a major cause of familial ALS in the Finnish population".

Chromosome 9 locus was also found to be associated with ALS in a second Article. Ammar Al-Chalabi from King's College London, UK, led an international team in a two-stage GWAS to try and identify genetic variations responsible for increased risk of ALS. The researchers began by examining DNA samples from 599 patients with sporadic ALS and 4144 controls from the UK. They analysed SNPs to test previously reported genetic associations for ALS risk. Two specific genetic markers (rs3849942 and rs2814707) showed an association with sporadic ALS, both located on chromosome 9p.

To search for new genetic signals that would otherwise be difficult to detect, the researchers also did a joint analysis (the largest GWAS of ALS to date), combining the UK samples with an additional 4312 patients with ALS and 8425 controls from seven other countries.

Chromosome 9p21.2 was the only significantly associated locus identified; this locus has also been previously linked with frontotemporal dementia. Importantly, none of the SNPs in the ITPR2, FGGY, DPP6, and UNC13A genes previously reported to be associated with ALS achieved significance. The authors say that the lack of replication of previously associated SNPs suggests that these might have been false-positive or population-specific results.

The authors conclude: "We have found strong evidence of a genetic association of two single SNPs on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS."

In a Comment, Guy Rouleau and colleagues from the University of Montreal in Canada say: "Although the results presented here must be interpreted with caution, both studies identified a linkage disequilibrium block in the chromosome 9p21 locus, suggesting that a variant in this genomic interval might have a role in ALS and possibly frontotemporal dementia. However, because patients with familial chromosome 9p-linked ALS—frontotemporal dementia do not share a common haplotype, multiple variations, and thus multiple founders, are probably involved."

Explore further: First genetic link discovered to difficult-to-diagnose breast cancer sub-type

More information:

add to favorites email to friend print save as pdf

Related Stories

International ALS gene search begins

May 16, 2006

U.S. scientists are leading the first international gene search for typical ALS -- amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

Researchers discover genetic link between both types of ALS

May 05, 2010

Researchers from Northwestern University Feinberg School of Medicine have discovered a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig's ...

Genetics of ALS progression

Jun 01, 2008

An upcoming paper in the June 1 issue of G&D, from Drs. Hidenori Ichijo and Hideki Nishitoh (University of Tokyo) and colleagues, lends new and valuable insight into the genetics of ALS.

Gene hunters close in on Lou Gehrig’s disease

Feb 21, 2007

In the first genome-wide search for the genetic roots of the most common form of amyotrophic lateral sclerosis (ALS), Johns Hopkins scientists have newly identified 34 unique variations in the human genetic code among 276 ...

Recommended for you

Refining the language for chromosomes

Apr 17, 2014

When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in ...

Down's chromosome cause genome-wide disruption

Apr 16, 2014

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.