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 in the clusterin gene and in the PICALM gene are both associated with risk for Alzheimer’s. A French team, lead by Philippe Amouyel, also found strong evidence for an association between and Alzheimer’s risk, and suggestive evidence for an association with .In addition, Amouyel’s research revealed that the A version of 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.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.———– 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.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.
  • Phantom

    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.

  • reno


    Does the new genotyping platform you started using a few days ago solve this problem ?

    • Hi reno,

      We can’t guarantee that the new platform will solve the problem but it was one of the things we worked on specifically. We should know whether we can determine APOE status reliably with the new platform in a couple of months.

  • Andy

    My father has had stents placed recently for a heart attack. I was also hoping that the APOe status could be honed in on more. I understand that by testing a broad range of genes that it is not possible to focus in on one specific gene,O but does this mean that we cannot acurately know if we are APOe (1,2,3,4) if we take this test? Or, does it mean that we will not be 100% sure that we have diagnosed the correct form of the gene. I only say this because I wouldn’t want to take the information into a treatment regeim without knowing 100% if the test is accurate, kind of risky. Thank you for all your help.

    Andy (I apologize for any mispelled words)

    • ScottH

      Thanks for the note. 23andMe’s test does indeed give your status for variants in the APOE gene that are relevant for determining Alzheimer’s risk. The APOE gene comes in three main variants: ε2, ε3, and ε4. APOE ε3 is the most common variant. APOE ε4 is associated with increased risk of AD, and ε2 is a rare variant of the gene that may have protective effects against AD. The reports we provide identify these variants and report the risk assessments associated with the different variants.