Could a genetic test have told me I was at a higher risk for developing type 2 diabetes? Image source: aldenchadwick

Metabolic syndrome isn’t quite as scary as it sounds.  Basically I am on my way to type 2 diabetes.  But if I eat better and get off the couch, I should stave off the disease and get better.

My question, naturally, is whether or not a genetic test could have told me I was at a higher risk for developing type 2 diabetes.  And whether I would have done anything with that result.

As you know if you’ve been following my blog, I took a 23andMe genetic test and have been writing about it since.  The image below shows what the front page of my clinical report looks like (click to enlarge):

According to the DNA checked in this test, I am in the average risk range for type 2 diabetes.  This doesn’t really seem to line up with my reality.  But I might not expect it to since these genetic tests are so limited right now.

This kind of test can be informative with the yes answer—yes I carry a certain version of a gene that might lead to a disease.  But the no answer isn’t that useful.  It doesn’t mean that they've looked at all the possible genetic differences that can lead to a disease and I don’t have any of them.  Basically it means that they didn’t find the specific genetic difference they were looking for.

Now I wouldn’t necessarily have predicted that any genetic test available right now could tell me a lot more than that.  Type 2 diabetes is too complicated for that and a whole lot more research will need to be done to get a genetic test useful to lots of people.

But still, this is probably what people are looking for with these sorts of genetic tests.  Will I get cancer, type 2 diabetes, Alzheimer’s, Parkinson’s, etc.?  For most of these cases, the tests can tell you a lot about rare forms of these diseases but little about the more common forms.

So the no answer didn’t really help me much.  Here I am on my way to being a diabetic and the test said I was at average risk.  Of course, I suppose I didn’t even need to take a test… all four of my grandparents came down with type 2 diabetes.  Like lots of these complex diseases, family history is the best predictor.

The second part of my question is a hypothetical one.  Let’s say they had a perfect genetic test that said that I was at an increased risk for type 2 diabetes.  Would it have changed my behavior?  I’m not sure but probably not.

I certainly wouldn’t have changed any of my behaviors when I was young.  I was invincible, remember?

Now that I’m a bit older, such a test might have influenced my behavior a bit.  I already knew about my risk because of my grandparents but my thought has always been that maybe I got lucky and didn’t inherit their tendencies towards diabetes.  But if they were tested and we shared the same genetic differences that led to type 2 diabetes, then I might be worried enough to change what I was doing.

Most likely though, my behavior modification wouldn’t be perfect.  What I’d probably do is keep watching TV and eating Twinkies but get my blood sugar tested more often.  Once I was headed for diabetes, then I’d modify my behavior and keep it at bay.  (I’m sure doctors scream into their pillows at night because of patients like me.)

This is different than some people’s reactions to other genetic tests.  For example, some women who find out they have the version of BRCA1 that greatly increases their chances of breast and ovarian cancer have a double mastectomy and/or a hysterectomy before there are any signs of cancer.

I might react much more strongly with a valid cancer genetic test.  Cancer is scary, nasty and not really reversible.  Type 2 diabetes is different.  You can start down the road, modify your behavior and then nip it in the bud.  Carpe diem and then pay the piper.

Genetic tests often don’t give as much information as you might think.

All sorts of goodies to try out!  I feel like a kid at Christmas.

The first thing I thought I’d do is check out my ancestry.  My grandfather’s grandmother was supposedly Native American and so I wanted to find out if I could see that in my DNA.  (This relates to my supposed relationship with the outlaw Sam Starr but that is a different story.)

23andMe has this Native American testing app in their 23andMe Labs section.  I clicked on my data and up popped this result:

Recent Native American ancestry is unlikely

Has it all been lies?  My great, great grandma wasn’t Native American?  Not so fast…

A “no” answer on a genetics test doesn’t necessarily tell you a lot.  (And sometimes, the “yes” answer isn’t so helpful either!)   Now as a geneticist, I know the drawbacks of ancestry tests like these.  What I wanted to see was if 23andMe did a good job of explaining them.

I first checked out my mitochondrial DNA (mtDNA) and my Y chromosome data.  These DNA don’t change a lot from generation to generation and so are really good at tracing ancestry many generations back.  Their downside for me is how they are passed down.

The Y chromosome passes from father to sons.  My great, great grandma didn’t have a Y to pass on so of course my Y chromosome data wouldn’t show that she was Native American.

mtDNA passes from mom to her children.  At first this sounds promising since we are talking about my great, great grandma until we realize that I am related to this woman through my grandfather.  His mtDNA died with him (except for his female relatives and their descendants) so that is lost to me as well.

Here is what 23andMe has written under interpretation of my mtDNA and Y chromosome results:

This mitochondrial DNA haplogroup is inconsistent with Native American ancestry along the maternal (mother's mother's mother's …) line.

This Y chromosome haplogroup is inconsistent with Native American ancestry along the paternal (father's father's father's …) line.

I suppose this says what I just said but I am not sure how many people would really appreciate the limitations of mtDNA and Y chromosome data from this explanation.  There wasn’t a link to a more explicit discussion of the limitations of this sort of testing and there wasn’t anything I could see from a quick glance at the ancestry part of the site either.  An explicit explanation would be good or maybe a figure like this one:

To me, this drives home the point that there is a whole lot of missing ancestry.  It might help if they had some sort of family tree app where you could indicate as much as you know about family relationships.  Once you’ve inputted the data, it would spit out what tests results would be useful to look at.

So the mtDNA and Y chromosome test results are of little use to me in this quest.  (And of little use to me in general as it confirms my pasty whiteness.)  Next blog I’ll deal with the rest of my DNA and what that can and can’t tell me about my great, great grandma.

The paint on this piggy bank tested for lead at 7253 parts per million (ppm); that is 11 times higher than the legal limit for lead paint.

Editor's Note: This week we have the first of two special reports on lead.

As a parent, there is a lot to worry about when it comes to the safety of my kids. Lead wasn't high on my list. Lead poisoning in children has dropped significantly in recent decades since the ban on lead-based paint in homes and the phase-out of leaded gasoline. Then came the record toy recalls of 2007, where millions of imported items coated in lead paint and made by household names like Mattel and Fisher Price violated the 30-year-old lead law.

Suddenly, parents, including me, eyed the toys in our homes and on store shelves with suspicion. Extensive research links lead exposure in children to lower IQ scores, neurological and behavioral problems, even anemia.

The toy recalls prompted congress to pass the Consumer Product Safety Improvement Act of 2008.

The Act not only lowers limits for lead and bans certain kinds of phthalates–it makes manufacturers and distributors accountable for products sold to American consumers by requiring items to be certified by third-party labs. But the testing, or certification piece of the Act, was postponed for a year. That raised a lot of questions for me as a reporter and as a parent.

I contacted the Center for Environmental Health, which researches lead, and other toxics, in consumer items and has sued manufacturers and distributors for violating standards.

CEH and KQED were interested in looking at what's sold at discount chains and 99 cent stores because of the history of previous recalls. CEH, through its regular spot testing, also thought that many of the larger retail outlets seem to have improved their process to weed out lead in children's items after the 2007 recalls.

I got some tips from CEH about potentially problematic products to look for. We purchased about 200 items and then CEH did the first round of testing using an X-ray fluorescence (XRF) device. The XRF is a handy tool used by a lot of commercial lead inspectors. It shoots high-energy x-rays at the item and sends back a chemical analysis, including the lead content.

Most items that exceeded the lead limits (600 parts per million) set by the Consumer Product Safety Improvement Act using the XRF device were then sent to a federally-accredited lab, MACS in Hayward, for detailed testing. At the lab, the parts or components that exceeded the lead limits were cut or scraped off and dissolved in an acid solution. Then tests were run to determine the lead content.

View a slide show of several of the items that violate the new lead limits below. We've also put together a list of items that violate the new lead limits, along with the test results.

So how can parents keep leaded toys away from kids? In addition to avoiding vinyl products, stay away from metal jewelry.

If you can, choose natural wood toys instead of painted items, especially if they are in yellow. Check the recall list posted by the Consumer Product Safety Commission. Many companies sell home lead test kits for consumer products. They're not 100-percent reliable and can give false negatives-and false positives too. If you're really concerned about your child's lead level, the best thing to do is to get a blood lead test.

Listen to the Playing with Lead – Part 1 radio report online.

Testing for Down syndrome may get much safer in the near future

This test will get around the small but very real risk of miscarriage that comes with more invasive forms of testing like amniocentesis. Instead of inserting a needle through mom’s belly and into the amniotic sac, a doctor will insert a needle into her arm. This is obviously much safer for the fetus.

The test won’t be able to find everything though. It can’t find subtle genetic mutations like those that cause cystic fibrosis or sickle cell anemia.

What the test can do is identify fetuses with extra chromosomes. This is one of the main reasons women get prenatal testing–to screen for diseases like Down, Edward's or Patau syndrome. Each one of these is due to an extra chromosome that the test can detect.

The test is actually marvelously simple. A sample of blood is taken from mom and the cells are removed. The researchers then take a close look at the DNA that is left behind. Most of this DNA comes from mom but some comes from the fetus too.

The researchers then figure out what millions of bits of the DNA look like. Next they match the bits of DNA to the chromosomes they came from. If more of the DNA bits match a certain chromosome than expected, then there is most likely an extra copy of that particular chromosome.

Think about it this way. Imagine a bag full of 23 different colored marbles where each color represents one human chromosome. You pull out marbles millions of times and then tally up the colors you get. (This can either be a ginormous bag or you can put the marbles back in once you pick one.)

If you pick more blue marbles, then there were probably more blue ones in the bag to start with. Of course this only works if you pick marbles many, many times.

Instead of using marbles, the researchers looked at the millions of bits of DNA they collected. They found that if there was an extra chromosome, then DNA bits from that chromosome were overrepresented. For example, they found that the 9 Down syndrome pregnancies they looked at had anywhere from 4-18% more chromosome 21 DNA than normal pregnancies*.

The 4% number was good enough to find pregnancies with extra chromosomes in this small study. They’ll need to repeat it in a larger study to turn this great idea into a diagnostic test for the public.

The test costs about 700 dollars to run right now but as sequencing gets cheaper (and it will), that cost should go way down. Also, right now they had to wait for the 14th week (which is a bit earlier than the 15-18 weeks for an amnio). Hopefully they’ll be able to improve the method to get testing done even earlier.

*The reason they didn’t get 50% more (as you might expect from having an extra chromosome) is that the fetal DNA made up only a small fraction of the DNA in the sample. In other words, most of the DNA was mom's.

So much information, so little understandingOn June 9, the California Department of Public Health (CDPH) sent letters to 13 different direct-to-consumer genetic testing companies telling them that they were not in compliance with California laws and needed to stop providing testing. The two main issues appear to be:

1. The testing facilities were not licensed correctly.
2. The tests were ordered without the request or counsel of a doctor.

This seems to me to be the opening salvo in an upcoming war between the government and these companies about DNA testing. The government wants to protect the consumer from getting incorrect results and/or misinterpreting the results they get. The companies want to provide people with information about their own DNA. I have to say I am unsure where I stand on this one.

On the one hand, there are some companies out there selling snake oil. For example, anyone claiming that they can provide a set of nutritional products based on your genetic test results almost certainly should be shut down.

And I would guess that the CDPH is not going after purely recreational companies like those involved in ancestry. I can't imagine why a doctor would order that kind of test. If these letters target ancestry companies, then whatever laws are involved should be changed.

There are also companies that comply with the current California laws. One of the most prominent is DNA Direct. This company follows all of the rules of the state, only offers well validated tests that are performed in a CLIA lab, and provides genetic counseling so people can understand the results they get.

But what about the companies between DNA Direct and ancestry testing services? Although we don't know for sure, the CDPH seems to have targeted many newer companies that look at hundreds of thousands or even millions of DNA differences at once throughout a person's DNA.

The three main companies that I know about that are in this gray region are Navigenics, 23andMe, and deCODEme. Navigenics is a different sort of beast from the other two in that it only provides information on DNA differences that have a well established link to a disease and they also provide genetic counseling. The other two can really be thought more of as recreational genomics at this point.

23andMe and deCODEme give a client all of their information and then tell the client what is known about each DNA difference. They offer ancestry, trait, and disease information bundled up in a single 1000 dollar test.

These companies count on the consumer being able to digest all of that data and recognize what is a strong and/or important correlation and what is not. This is the point where a group that includes the government, doctors, and many academics differ with these companies.

Once we make sure that the testing is done well, the question really boils down to whether or not the consumer can handle all of the information*. Can consumers interpret these kinds of results and know when to seek help and when not to?

The answer is that some can and some can't. So how do we protect those who can't but still allow people access to their own DNA? Or should we protect consumers at all from their own DNA information?

*There is also the stipulation about a doctor ordering the test but frankly I don't get that one and am not sure it should be part of any consumer protection.

Copy of the letter from Wired Science