Maybe this has recently happened to you: You’ve just received your DNA test results from some genetic testing company. Now, armed with this raw genomic data, you’re ready to make gripping discoveries about yourself.
So you load up your genomic data into a tool like GENOME LINK, and scan your eyes over the dashboard, eager to see what the data is going to tell you. That’s when you notice something: according to your genomic data, you are quite likely to be a morning person — no double shot of espresso needed to kick you into action when the sun comes up.
But you know, for yourself, that you are anything but a morning person. On the contrary, you love sleeping in.
Inevitably, this raises the question: How do you make sense of such a discrepancy — where your DNA suggests that you are a morning person, but you really, really don’t feel like one?
Of course, this is just one example of a DNA test leading to a conclusion that conflicts with what you know to be true about yourself. This can happen for many other traits, too.
If something similar has happened to you, you aren’t alone.
In fact, many users of consumer genetic tests are often surprised when they get results from genetic tests that don’t completely line up with their actual traits.
Why is this the case? Why are such genetic tests not always completely accurate? 🤔
Unraveling the answer to this question requires taking a good look at how genetic testing for a given trait works.
It All Begins With Something Called a GWA Study
Before any trait can be linked to a specific genome sequence or genetic marker, a genome-wide association (GWA) study must be done. In such a study, the genome sequences of a large number of people are analyzed.
For the sake of illustration, let’s say there’s a GWA study that identifies the below genetic sequences in 5 different people at a given location in their genomes — a location involved in determining eye color:
Person 1: TGCTACCAGT
Person 2: TGCTACCAGT
Person 3: TGCTACCAGT
Person 4: TGCTACCAGT
Person 5: TGCTGCCAGT
You might recall that DNA consists of four bases, represented by the letters A, C, G, and T. That’s why the genetic sequences above use these four letters.
Now, examine those hypothetical sequences and you’ll notice they’re all the same — except that “Person 5” has a slight variation: a “G” (in bold) in the 5th letter. All the other people have an A at that position.
Let’s further suppose that all of these people have brown eyes — with the sole exception of Person 5, who has blue eyes.
From here, it could be preliminarily hypothesized that anyone with a “G” at that position has blue eyes. Of course, this result must be validated with and strengthened by additional studies. These studies should replicate the findings of the first study with statistical significance, and involve more research participants.
The example above is a highly simplified example of how correlations are drawn between genetic markers and physical traits. But it showcases the basic methodology researchers use to find genetic markers that seem linked to particular traits.
However, the method is not a perfect tool for gleaning personal insights on one’s biology. It’s possible to have a “marker” in your genome which suggests you have a certain trait — when, in fact, you do not have that trait.
The reason? Because correlation isn’t causation.
Correlation is Not Causation
Even if there’s a correlation between a specific genetic marker and a trait, it doesn’t mean that the genetic marker is actually biologically involved in determining that trait. GWA studies have found some genetic markers that tend to be associated with particular traits, based on large population studies. The key here is that the correlation between genetic marker and trait holds true most of the time for most people, but the correlation almost certainly will not hold for some people.
In other words, it is not deterministic: having that genetic marker does not guarantee you’ll have the trait. Rather, it just raises your chances for having or not having the certain trait.
While most non-medical human traits fall into the above category, keep in mind that many human herditary diseases are determined by single point mutations in the genome. An example is sickle cell anemia. You have sickle cell anemia without doubt if you test positive for both copies of this genetic marker.
Other Reasons Why DNA Test Results Don’t Always Match Your Actual Traits
Many of the traits we’re interested in, such as longevity, obesity, height, and intelligence are shaped by complex biological pathways, many of which researchers still do not fully understand. These complex traits tend to be associated with many, many known genetic markers. And more genetic markers of unpredictable influencing power over the trait may be identified in the future.
Moreover, these traits are also influenced by our environment and personal choices, so looking at just our genes is not enough. Consider this scenario: according to your genetic tests, you shouldn’t have ADHD (attention-deficit/hyperactivity disorder). Yet your psychiatrist diagnoses you with ADHD. How can this be possible? As it turns out, while ADHD is predominantly caused by genetics, some environmental factors can also contribute to ADHD — such as prenatal exposure to heavy metals.
With so many inputs factoring into the outcome of the trait — none of which are deterministic — we can and should expect some margin of error, and that DNA test results are science’s current “best guess” based on the limited information from our DNA.
There’s also the issue that many GWA studies use sample populations that are primarily Caucasian. This can skew the results if you aren’t Caucasian. Fortunately, you can take this into consideration with a tool like GENOME LINK by filtering for studies that focus on your ethnicity.
DNA Testing is a Piece of a Puzzle
While GWA studies are often effective at uncovering meaningful links between genetic markers and traits, they aren’t always 100% accurate when their results are applied to one’s personal biology.
So if genetic tests aren’t always accurate, does that mean they should be discarded as useless?
Absolutely not. Instead, it’s best to simply understand that DNA test results are simply a piece in the greater puzzle that is your total biology. Researchers who undertake GWA studies put in a great deal of effort to eliminate false positives, so these studies can and do shed a useful light on personal genetics.
There’s more good news, too: more and more studies on human genomics keep coming out (fueled by the ever-decreasing cost of whole-genome sequencing) using better population samples than ever before. This means that the accuracy of tools like GENOME LINK will only rise, giving you more meaning and insight into what your genome is really telling you.