Sep 08 2009
SNPwatch: Largest Alzheimer’s Genetic Studies To Date Identify Three New Susceptibility Genes
Despite years of effort and millions of dollars in research funding, only one gene, APOE, has been conclusively associated with Alzheimer’s disease risk so far. But now the results of two of the largest Alzheimer’s studies ever provide convincing evidence that three more genes affect risk for the disease.
“These findings are a leap forward for dementia research. At a time when we are yet to find ways of halting this devastating condition, this development is likely to spark off numerous new ideas, collaborations and more in the race for a cure,” said a statement from Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust in the UK.
A British team, led by Julie Williams, found strong evidence that rs11136000 in the clusterin gene and rs3851179 in the PICALM gene are both associated with risk for Alzheimer’s. For both SNPs, each copy of the less common T version decreased the odds of having late-onset Alzheimer’s by 0.86 times compared to two Cs.
(This is correct. The versions and effects of the two SNPs really did turn out to be exactly the same. 23andMe customers can check their data for both SNPs using the links to the Browse Raw Data feature above.)
A French team, lead by Philippe Amouyel, also found strong evidence for an association between rs11136000 and Alzheimer’s risk, and suggestive evidence for an association with rs3851179.
In addition, Amouyel’s research revealed that the A version of rs6656401 in the CR1 gene increases the odds of Alzheimer’s by 1.21 times. Suggestive evidence for this association was also seen in the work of Williams’ group.
(23andMe cannot offer information about rs6656401 at this time.)
The results from both teams were published online this week in the journal Nature Genetics.
Williams said in a statement that the number of people who fall victim to Alzheimer’s could be reduced by 20% if treatments addressing the effects of the three newly identified genes could be found.
The proteins made by the clusterin and CR1 genes are known to play a part in clearing out amyloid beta, the protein that forms plaques in the brains of people with Alzheimer’s. PICALM encodes a protein important for proper communication between brain cells, a process that is known to be disturbed in Alzheimer’s patients.
In total, the DNA of more than 10,000 people with Alzheimer’s disease and more than 18,000 controls from ten countries was analyzed by the two teams of researchers. But both groups agree that there is still much more to find. Williams’ team is already planning an even larger study involving 60,000 people that she believes can be completed within the next year.
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Alzheimer’s, the most common cause of dementia in people 65 years and older, currently affects about five million people in the United States. As the population ages, many more people are expected to be afflicted; some estimate 14 million Americans will have Alzheimer’s by the year 2050.
(For technical reasons, 23andMe cannot currently give customers information about their APOE status. Our scientists are actively working on this problem.)
SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.
2 Responses to “SNPwatch: Largest Alzheimer’s Genetic Studies To Date Identify Three New Susceptibility Genes”
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Great blog post.
It could be interesting to have a more detailed blog post about what “technical reasons” prevent you from giving out APOE status, what solutions are possible, why that particular SNP is more problematic to sequence than others, etc.
Phantom,
Thanks for reading the Spittoon. We’re not planning to do a post like that, but I can say a few words about the difficulties of genotyping the SNP that determines APOE status (rs429358).
Some parts of the genome are especially difficult to read due to the sequence and/or structure of the DNA molecule in those regions. As luck would have it, that’s the case with the part of chromosome 19 near rs429358.
There are ways to genotype rs429358 by zeroing in on it specifically. But our genotyping platform is optimized to provide accurate results at more than 500,000 locations across the genome, not at any one location in particular.
We can make an educated guess about a person’s genotype at rs429358 based on the data we do collect, and get the correct result in the majority of cases. But our goal is to provide accurate genetic information for everyone across the genome; we want to have near-perfect genotyping for rs429358 before we start giving customers their APOE results. We expect to be able to do that soon.