Many genetic tests just uncover one small bit of
your disease risk formula.
Image courtesy of Tungsten

Since 23andMe is offering data on Alzheimer’s risk but only with an upgrade, I decided to get that upgrade. I got the new results last week and opened it right up. There was a new Alzheimer’s link with a little lock on it.

The lock is to keep me out until I feel ready to deal with the news. Well, I’m ready…

When I opened the lock, I was given information about one gene, APOE. This was pretty disappointing. In my case, I was able to guess my APOE status with the old information.

I understand that for people who couldn’t guess their APOE status before that these new results might be useful. But I expected more. Lots of genes all impact our risk of getting Alzheimer’s and scientists are making real progress figuring these out.

What I was hoping to see was a compilation of all the information out there. See, my APOE data suggests that I am at a lower risk. But what if all my other genes are of the wrong type and put me at a higher risk? Then I might be at a higher risk than I think I am.

And my situation is better than people who have APOE gene versions that put them at a higher risk. What if all of their other genes put them at a lower risk? Now they are worried for no reason.

This points to one of the big issues with genetic tests and complex genetic diseases. Right now we know a bit about some of the genes involved but we don’t yet know the whole story.

It is kind of like having a whiteboard with a vast, awful, Jimmy Neutronesque formula scrawled across it. This is our genetic risk for getting something like Alzheimer’s.

Unfortunately, a blanket of ignorance hides most of the formula from us. We can only get a glimpse of one small part of it. What we then try to do is figure out our risk from that glimpse.

So let’s say we manage to uncover a bit of the blanket in the corner and we see a 0.5X. Does that mean that I am half as likely to get Alzheimer’s? Hardly. We have managed to see a piece of the whole formula but the rest remains hidden.

My APOE status is really just a bit of the formula for my Alzheimer’s risk peeking out from under the blanket. I don’t know the rest of the formula and so don’t know the rest of the risk.

APOE status is a well-studied risk that we know a lot about. We have completely uncovered it on our whiteboard. Some studies are staring to reveal other parts of the board but they aren’t completely clear yet. This is probably why 23andMe left them out.

I decided to look at the hazy parts of my equation using good old SNPedia. Remember, they have lots of information about DNA variants and disease that isn’t as filtered as is 23andMe’s.

Here is what I found when I put my data from 23andMe through SNPedia. I have listed the SNP, what I have at the SNP (the allele), and my risk for Alzheimer’s for those that give me a higher or lower chance for Alzheimer’s. I haven’t put in the ones that have normal risk.

I came out very well here. I am at a much lower risk for getting Alzheimer’s when I look at these SNPs. Yay!

But what if I just had s4934 data? I would come out thinking I was at a higher risk when I am actually at a lower one. Lots of needless worry over nothing…

Now I shouldn’t get complacent, this is still only a bit of my risk for Alzheimer’s. There may be some killer SNP lurking in my DNA, ready to spring Alzheimer’s on me. Or a long list of small, not-yet-discovered SNPs that will eat away at my supposed lower risk for Alzheimer’s. We just don’t know yet.

And I haven’t even begun to talk about environmental impacts. We know so little about that one with Alzheimer’s that we haven’t even found the whiteboard yet!

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When talking about genetic pre-disposition to a condition, make sure you understand both the increased risk factor and the general risk.

What I try to do in answering these questions is give them a feel for what the disease is, how genes are involved and then give them some links to some reliable websites on the topic.  I always try to emphasize that for a lot of diseases, genes are just one part of the story and that speaking with a genetic counselor in person might be a good idea.  I also warn them to look very carefully at the risk numbers.

Very often risks are given in how much more likely someone is to get a disease compared to the general public.  So, for example, if you have a brother or sister with schizophrenia, then you can be up to 9 times more likely to end up with the disease too.  Sounds like a scary number!  But it may not be…

If the general risk is 1 in a million, then 9 times is pretty insignificant.  It means that your risk is 1 in 110,000 or so.  This is worse than the chances of dating a supermodel (1 in 87,000) or of winning the lottery if you buy 50 tickets (1 in 77,000).  So if this were the case, a 9 fold increase means you still probably aren't getting the disease.

For schizophrenia, the general risk is 1 in 100.  This means that if you have a parent or sibling with the disease, your chances go up to about 1 in 11.  Unfortunately 9 times more likely looks pretty significant here…

Sometimes, though, a smaller risk can be even more significant.  For example, women who have a sister, mother, or daughter with breast cancer are twice as likely to develop breast cancer themselves.  Since about 12% of women will develop breast cancer in their lifetime, this means the risk is actually 24% or about 1 in 4.

So when investigating these sorts of risks, get both numbers.  You want to know what your increased risk is because a relative has the condition AND what the general risk is.  These two numbers together will give you a better feel for your chances.

An important note here is that these risks are averages.  Your actual chances will depend on the genes you have, how you live your life, etc..  For example, some of the women is the breast cancer example carry certain versions of the BRCA1 or BRCA2 gene.  These women are 5 times more likely to develop breast cancer pushes their risk to around 60%.

This is one of the many reasons why a sitdown with a genetic counselor is so useful.  Your risk depends on your specific situation and not an average risk you find on the internet.  A genetic counselor can take the time to carefully go over your family history and let you know what tests are available so you can better calculate your odds.

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