23andMe's DNA testing was always fun. Now it is more useful as well.

As anyone who follows this blog knows, I had my DNA tested awhile back by a company called 23andMe.  I wrote about what I learned and didn’t learn from their testing in a bunch of blog entries.

In my mind 23andMe has always been a sort of recreational genetics testing company.  You can find out about your earwax, whether you are likely to have blue eyes or be lactose intolerant and lots of other minor sorts of traits.  This is stuff you probably already know but for geeks it is pretty cool to see them written out in their DNA.

The company always offered some health data too but it wasn’t that strong.  For example, they could tell you if you carried the most common DNA difference that could lead to cystic fibrosis (CF) but not about the less common ones.  In fact, I gave them an incomplete for their carrier testing a few months back.

Since then, the company has gone away from being a place where you get your DNA tested for coolness’ sake to one with a focus on health and/or ancestry.  With this change has come a much-improved product for people interested in what their DNA tells them about their carrier status for a variety of genetic diseases.

Carrier status is important if you are considering having a child.  If you and your partner both carry the broken versions of a gene that could lead to a disease, then your child would be at an increased risk for getting that disease.  For example, if both you and your partner have a nonworking copy of the CFTR gene, then, depending on the exact DNA you each have, your child could have up to a 25% chance of ending up with CF.

This is why the first iteration of 23andMe carrier testing wasn’t as useful as I would have liked.  They tested only one of the 100’s of different DNA variants in the CFTR gene that can lead to CF. Since this DNA variant only accounts for about half the cases of CF, there was a good chance that something would get missed.  This is no longer true.

As part of the refocusing, 23andMe looks for 31 different variants in the CFTR gene that are known to cause CF. Now this isn’t hundreds but is more than the 23 recommended by the American College of Medical Genetics.  And in fact 23andMe includes these 23 in the 31 it tests.

Of course the testing still isn’t perfect but no testing is.  Some of the tests are only useful for certain ethnic groups.  And there is no upfront genetic counseling to help you decide whether or not genetic testing would be useful in your situation anyway.

But the bottom line is that 23andMe’s testing for genetic diseases that you might be carrying is much stronger than it was before.  So much so that it can even give you some piece of mind for many of these diseases.

In some ways I’ll miss the more whimsical look at DNA that 23andMe used to represent.  But this obviously wasn’t a good business model for anyone except those enamored of DNA.  And 23andMe does need to make a profit…

For most of us, avoiding these is just as important as the genes we inherit.

As someone who studies genes, I tend to give the environment short shrift. I have to watch out for that because it can cause a blind spot in how I think about biology. And how I live my life.

As readers of this blog might remember, I was recently diagnosed with metabolic syndrome just as I was undergoing DNA testing. This was a wake up call in a couple of different ways.

First off, it confirmed my belief that we can’t get a lot out of genetic testing for complicated diseases right now. I couldn’t look at my DNA and predict that I would end up with high cholesterol, triglycerides and glucose levels. We just don’t know enough yet about our genes to be able to figure this out from any available DNA test.

But I could have guessed this might be a problem from my lifestyle and family history. All four of my grandparents developed Type 2 diabetes which put me at a pretty high risk. Of course I thought I could beat the odds and so lived a life filled with couch sitting, Haagen Dazs, and Double Western Bacon Cheeseburgers (cue Homer Simpson drool). Until my diagnosis.

Then I decided to see if all this talk of diet and exercise actually can have a significant impact on me. Or was I destined to high cholesterol, triglycerides and glucose levels because of the genes I got from my parents.

The doctor told me to lose weight, exercise more and eat better. So I did.

I lost 30 pounds by changing my diet and walking 30 minutes a day. This dropped my body mass index (BMI) from overweight (27.8) to normal (23.5).

I also stopped eating most sweets, and cut my saturated fats down to 15 grams per day. And the effects on my blood work have been amazing.

Here are a few of the stats:

As you can see, everything is now in the normal range except for glucose which is still a bit worrisome. Now I just need to maintain this regimen which, in America, won’t be easy.

I probably panicked and went overboard anyway. I should have tried to just add exercise and see if that was good enough. If not, then cut back on sweets and saturated fats. I did bad science on myself by changing too many variables at once.

I think what I can conclude is that my set of genes makes me particularly susceptible to my lifestyle choices. Some lucky people are born with genes that let them get away with poor diet and no exercise.

I am not one of those lucky ones. Although perhaps more lucky than those people who make these changes and still have these health issues.

You've probably heard about some of the breakthroughs in personal genome sequencing, where companies take a look at your DNA and send back your risk profile. That can be confusing information to have (check out this post from Quest blogger Dr. Barry Starr for his take on it). But there's a flip side to all this genetic research that doesn't have to do with risk: personalized medicine. That's where doctors can customize medical treatments to fit your genetic profile.

Right now, there are only a handful of drugs that are labeled with genetic information, so doctors can take it into consideration. (Here's an article from the New York Times that gives an overview).  But that doesn't mean existing medications are left out.  I spent some time with Deanna Kroetz in this story, who studies pharmacogenomics at UC San Francisco.  She explained that differences in our DNA can cause some of us to process drugs at different rates. We all metabolize drugs with enzymes in the liver, but based on expression of our DNA, we may have different levels of enzymes or our enzymes may not function as well.

There are plenty of other things that affect how we process drugs, like our diet or other drugs we're taking. But these genetic differences mean some people metabolize drugs quickly and others metabolize them slowly. One example that many people are familiar with is codeine.  Codeine is converted into morphine by our bodies and it's the morphine that actually has an effect — but that conversion depends on a particular enzyme. Some people have very low levels of the enzyme that's needed, so codeine doesn't do much for them.

They're also studying another drug response mechanism at UCSF and it has to do with our cells. Many drugs have to go inside our cells in order to have an effect, but if you think back to high school biology, you might remember that cells are protected by membranes.  It takes transporters – those special gatekeepers sitting on the cell membranes — to allow things in.  They also can spit things out of cells.

I spent some time in the lab with Rachel LaFond, a graduate student at UCSF.  She was running experiments on one particular transporter known as ABCG2. This transporter is particularly good at spitting things out of cells. Normally its job is to kick toxins out, but some cancers have been able to hijack this machinery.  Cancer cells with an over expression of this transporter can spit out chemotherapy drugs, which means they aren't helping the patient.  LaFond is working to understand this variation better, so they could one day develop a genetic test for it.

Listen to the Personalized Medicine radio report online.

Hopefully this DNA analysis data will be better at telling my future than tea leaves or goat entrails.

This is a test that will look at over 500,000 different spots on my DNA.  From the results I'll be able to learn about my future health and my past ancestry.  Well, as much as I can learn given the current state of genetic knowledge.

And there's the rub.  I have held off on doing this for quite awhile because I am just not sure how useful it will be.

Most of the DNA studies on the big diseases like schizophrenia, autism, diabetes, heart disease, etc. have not been that conclusive.  They tend to find bits of DNA that have a very small effect on risk.

Undoubtedly as more studies are done, we'll find lots of bits of DNA like this and we'll be able to figure out our risk more accurately by adding them all up.  But we're not there yet.  In fact we're probably years away from being able to do this.

I have also been a bit squeamish about sending my DNA to a company.  Yes, I know they'll be careful but still…it's my DNA.  You can't get any more personal than that!  I would hate for someone to get that information and use it against me (think insurance agent).

So why did I finally decide to go through with it?  One reason is that I get a lot of questions from people at the Ask a Geneticist site about how useful or good the test is.  Right now I have to tell them I don't know.  I'd like to be more helpful than that.

I also think that it will be fascinating to see all of my bits of DNA.  This is the stuff that is a big part of making me who I am.  It will be so cool to look into that crystal ball even if the future I see is a bit murky.

Of course as a big old science geek I'll be interested in that stuff…it's my bread and butter!  What I also want to do is try to imagine what the test is like for someone who doesn't go all gaga for genetics.  How is it for people who aren't necessarily mesmerized by the beauty of DNA and instead are mostly interested in diseases, traits, and ancestry?

I guess I'll find out soon.  I sent my spit in last week.  I'll keep you updated in future posts.