Studies Identify Five More Genetic Variants Associated with Alzheimer’s

Results published this week in the journal Nature Genetics identified five more genes associated with risk of developing Alzheimer’s, doubling the total number of genes known to be linked to the devastating disease. The two studies — one led by Paul Hollingworth and Julie Williams in Europe and the other by the Alzheimer’s Disease Genetics Consortium in the U.S. — analyzed DNA from more than 50,000 people of European ancestry. Altogether, the researchers identified five new genetic variants located near the ABCA7, MS4A4A, EPHA1, CD33, and CD2AP genes, which are each associated with a 10-15% increase or decrease in the odds of Alzheimer’s.

(23andMe customers can check their data for three of those five variants as well as four others previously identified using the Browse Raw Data feature and the table at the end of this post. Not all variants are available on all versions of 23andMe’s genotyping platform.)

While the effects of these genetic variants may not be strong, their discovery offers additional clues about the biological underpinnings of the disease. Combined with previous studies (see Spittoon posts here and here), the genes implicated suggest that biological pathways involved in the immune system and in the transport of cholesterol-related molecules may be important in the development of the disease.

As reported in the New York Times on Sunday, one of the new studies’ authors, Dr. Richard Mayeux, said the findings would help “open up the field.”

Although the studies published this week help fill in some gaps in our understanding of Alzheimer’s, the risks associated with the newly identified variants are still dwarfed by the risk associated with the well-established ε4 variant of the APOE gene. If a person inherits the APOE ε4 variant from one parent, his or her risk is two to four times higher than the average person’s. If that person inherits it from both parents the risk rises to more than 10 times greater than average. But as with all complex, multi-factorial conditions such as Alzheimer’s, the presence of a variant does not mean a person will definitely develop the disease.

Currently more than 5.4 million Americans have Alzheimer’s. The Alzheimer’s Association estimates that this year alone the cost of the disease will top $183 billion.

Genetic variants (excluding APOE e4) associated with late-onset Alzheimer’s

Variant Nearest Gene Version Odds Ratio
rs1562990* MS4A4A C 0.89
rs11767557 EPHA1 C 0.90
rs3865444 CD33 A 0.91
rs7561528 BIN1 A 1.17
rs561655 PICALM G 0.87
rs6701713 CR1 A 1.17
rs1532278 CLU T 0.89

*Equivalent to rs4938933 reported in the study

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.






  • Chris

    So 23andme does not gather data for the APOE ε4relevant SNPs on their chips?

    • http://23andme.com Shwu

      The SNP required to determine APOE ε4 did not perform up to our standards of quality control on the previous version of the genotyping platform (v2). It seems to be working much better on the latest version (v3) but still needs to pass several more checks before we can report on it. Stay tuned!

  • Vladimir and Maureen Markov

    Thank you for reporting on this here. M&V

  • Steve Tsuida

    The table above uses a single letter for the version associated with each SNP, but in our 23andme.com raw data the genotypes list two letters, which of the two matters in this case, or is it a matter of even having one match?

    (I just started using 23andme.com—my results went online on April 4th—and I’m totally new to to all things genetics, so that was probably a dumb question.)

    • http://23andme.com Shwu

      Hi Steve,

      The table includes the letter or version of the SNP that is associated with the odds ratio that is also listed in the table. So, for example, the “A” version of rs6701713 is associated with a change in odds of developing Alzheimer’s by a factor of 1.17. That means having one copy of an A there increases your odds by 1.17 times, and having two copies increases your odds by 1.17*1.17, or 1.37 times.

      Welcome to the service!

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