Personal Genetics Testing

Personal Genetics Testing

The Basics

One of the gifts people will be thinking about giving and getting this Christmas is a do-it-yourself (partly) personal genetics testing kit, otherwise known as a Direct To Consumer (DTC) genetics test kit. To help you decide whether it’s a good idea or not, I put together this little blog entry. Hope you find it helpful.

There are a number of commercial players in the field, most notably 23andme, Ancestry.com and MyHeritage, among others. All of these vendors provide information about your heritage, but only one (23and me) provides health related information, as explained below. Cost for tests are generally about $100, but closer to $200 for the 23andme test, since it provides a more comprehensive report. Watch out for discounts, however. Most of these vendors offer up to half off the price around the holidays, particularly on Black Friday.

How the testing works

The actual test procedure is simple. No blood involved! You just spit in a tube, add the supplied preservative, and mail the kit back to the company. Sometime later, typically a few weeks, they send you the results electronically, through access to your private account on the company website.

Essentially, the company labs have robotic machines and instruments that extract the DNA from the few cells that are in the saliva sample, having sloughed off your mouth tissue. As it turns out every cell of your body has the same DNA so it really does not matter what part of your body the sample came from. That’s also why forensic scientists can use hair, blood or semen samples to do genetic testing. Since our DNA composition does not change throughout life, the test results are good from the day you are conceived until death.

Once the DNA is extracted it’s replicated using a nifty procedure called “PCR” and analyzed. In essence, your DNA sample is compared to other DNA samples that come from people who have known geographic origin and known health conditions. It’s a kind of a matching game (genotyping), more than an analysis of the individual letters of your DNA alphabet (sequencing). For the most part, the DNA of individuals is identical by more than 99%. And this is important to believers because it affirms the truth of the bible that we are all human beings, we are all created in the image of God. There are no subspecies of people! But the small differences among us are what make us all unique and that’s what the tests look for. In general, genetic testing companies compare over 500,000 variations in a person’s genes as part of their testing.

Heritage/ancestry results

All personal genetics testing company reports include information about your genetic heritage (ancestry) for about five generations back. Generally you receive a breakdown of where your forefathers (and foremothers) originated as a table with percentages for each geographical region. The most accurate and precise results are for people of European decent, because those are the people most well characterized in the companies’ DNA matching database.

One interesting feature of the tests is that you can compare your results with those of family members. The extent to which two people have matching DNA depends on how close they are related. Parents and children have about 50% matching DNA, while first cousins have about 25% matching DNA.

The testing companies provide a means for you to opt in if you want to be alerted when possible relatives are identified from their test results. Of course, every now and then, it turns out that the test results for two supposedly related people have virtually no matching DNA. This can be something of a challenge when the people tested believe they are parent and child, leading to a “is that really you dad?” crisis. Of course for most of us, the easiest way to find out about our heritage and our relatives is to simply ask the people we already know in our family tree. For orphans it’s another matter.

Growth trend of DTC testing

Security

All of the three genetic testing companies mentioned earlier have strict internal confidentiality rules and they do not release personal genetic information to anyone, according to their corporate documentation and to the best of my knowledge. Any data they do share is anonymized so that it cannot be traced back to an individual. In fact, many participants in 23andme testing (about 80%) agree to answer questions about their health status so the company can make correlations that can potentially be used for drug development. Again, this information is not linked to the individual. In general, personal genetic information can be compromised when someone sends their genetic raw-data file to a third party, like Gedmatch. Many people do this as a way of finding relatives across testing companies. The stories you hear about in the media about the government tracking down criminals are based on these shared public platforms, not data obtained from the genetic testing companies themselves.

Of course the other aspect of security that people are often concerned about is the use of genetic data by an employer or health insurer. Fortunately, there is a federal law, the Genetic Information Nondiscrimination Act, often referred to as GINA, that explicitly prohibits the use of genetic information for assessing a person’s health insurance applicability or cost as well as for job hiring or job promotions. In my opinion, personal security in genetic testing is a bit of an overhyped issue.

Trait and Health Information

But heritage is not the only information that can be obtained from genetic testing. Information about your traits, health status, and disease susceptibility can also be teased out of the raw data and reported. And while all the testing companies determine essentially the same data set, only one company, 23andme, has authorization to release health information to the public based on that data. The reason for this is that 23anme took the time and made the effort to show the FDA that their health-related predictions are valid. For people who use the other genetic test companies, it is possible to get trait and health information by downloading your raw data file and sending it to a third party service, like Promethease, but there is less certainty about privacy and the correct interpretation of the genetic results.

What you get from 23andme is information regarding your traits, your carrier status, and your disease risks. We will look at each of these individually below. But there is a problem: It turns out that the relationship between health and genes is not as simple as what Mendel found for his peas. Most traits and diseases are polygenic, meaning that they are influenced by a number of genes working together in complex ways that are not precisely understood. Things like diabetes, heart disease, cancer, depression are not dependent on a single gene, even though trends can be seen within a family. So what you get from the genetic report is not deterministic but rather probabilistic, a type of educated guess, an estimation or your risk.

Traits

Traits are simply definable distinguishing characteristics for an individual. Most of the traits that can be predicted from genetics are, shall we say, inconsequential, like the ability to taste cilantro, and to curl your tongue. If you want to know if your and your spouces’ genetics predicts that your kids will be geniuses forget it, there are just too many genes involved and the science is not there yet. One trait that often gets people’s attention is the presence of fast and slow twitch fibers as predicted from genetics. The problem with this trait is that it has only a very tiny impact on ones sports performance, so it has very little value in helping a person decide which sports to enter.

Health Risks

Angelina Jolie chose to undergo a double mastectomy because she carries a mutation in the BRCA1 gene that greatly increased her risk of breast and ovarian cancer.

As mentioned earlier, a finding of a “health risk” does not mean that you will go on to develop the health problem in question. Rather, it means you have a statistically higher (or lower) chance of developing the problem. Generally the increase or decrease in risk is relatively small, somewhere between half to twice that of the general population. And of course, in almost all situations, your behaviors also factor into the risk, since both nature (genetics) and nurture (environment) factor into one’s health. A report may state that you are at 25% greater risk for obesity, but rest assured, reducing your caloric intake or increasing your caloric output can compensate for this tendency.

For a few genetic findings the risk can be higher, by as much as 10 fold, as in the case of Alzheimer’s disease and a particular type of breast cancer. In the case of breast cancer, the test is looking for particular variants of the BRCA gene that are highly associated with the development of the disease. The kicker is that, with the exception of women of Ashkenazi Jewish ancestry, most cases of breast cancer are unrelated to BRCA. Also not all the impactful variants of the BRCA gene are tested for. So a positive finding having a high-risk BRCA variant) is a strong signal that you might have a problem and you should see a physician for a confirmatory test. On the other hand a negative finding (not having a high-risk BRCA variant) does NOT rule out the possibility of developing breast cancer. If this seems confusing, it is. That’s why the FDA is reluctant to allow health information to be disseminated by genetic test providers.

Carrier Status

An interesting bit of information also provided by 23andme is disease carrier status. This is for conditions that are predominantly associated with a single gene (like Mendel’s peas) and are considered “recessive”. Two examples are cystic fibrosis and sickle cell anemia. If you have two bad copies of the gene you know it because you have the disease condition, but if you have one copy the condition is generally silent, you are a carrier. It can be useful to know if you are a carrier because marrying someone who is also a carrier gives a 1 in 4 chance that a child of the couple will have two bad copies of the gene and will manifest the actual disease. Generally speaking, though, the carrier status reporting involves diseases that are relatively rare, so it is unlikely that a person would use it to screen potential mates!

Conclusion

So what is the bottom line for personal genetic testing? Well, I would say it’s basically a recreational exercise at this point. Knowing your roots can be heartwarming and, for some, reassuring. Health wise, there is little most of us will gain that couldn’t be obtained from a careful family history. Indeed, that’s why your doctor asks about your mom and dad and not your 23andme results. But the ability to make predictions about health is improving and the testing companies send updates when new discoveries are made and applied to your genetic (raw) results on file. Also, as time goes on more precise DNA analysis, such as sequencing, will become available at an affordable price and will provide a more detailed and comprehensive picture of one’s genetic profile. In the meantime, why not have the test run and have some fun learning a little about yourself. If nothing else, just experiencing first-hand the impact of the amazing DNA molecule on our lives gives us an appreciation for the Psalmist’s thought “I praise you because I am fearfully and wonderfully made”.

A good although somewhat more technical review of personal genetics testing, in both text and audio format, can be found at the British Journal of Medicine website: https://www.bmj.com/content/367/bmj.l5688

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