In this post, we’ll review the basics of genetic testing and what to consider before having children tested. There’s a growing number of services that offer testing for children, and many parents are curious about the accuracy of these tests, their privacy, and other important issues.
Medical action should never be taken based on a genetic test without consulting a genetic counselor. These professionals can advise whether genetic testing is even necessary and are specifically trained to provide guidance based on clinical reports from a genetic test.
To understand genetic testing, it’s necessary to define a few terms:
- Genes. These are segments of DNA that have the genetic code for the proteins and enzymes that function in our bodies. Genes make up 1-2% of all our DNA.
- Genome. This describes all the DNA in a cell. In humans, our genome is inherited from our parents: roughly 50% from our mothers and 50% from our fathers.
- Variant or polymorphism. These are spots in our genome where we know that there’s variability in the DNA sequence between different people.
- Trait. A characteristic or aspect of us that is often genetically determined, such as eye color or height.
What is genetic testing?
Genetic testing is a medical test that can provide us with information about our DNA. It can tell us whether changes in our DNA can account for medical conditions. It can also provide information on our risk of developing medical conditions and whether our children might also inherit the condition.
There are also direct-to-consumer (DTC) tests that are for entertainment purposes as well as tests that have not been clinically validated. The most popular of these DTC tests are those that tell us about our ancestry/heritage such as tests developed by 23andMe and Ancestry.com. This post will focus on these direct-to-consumer tests.
How does genetic testing work?
There are various forms of genetic testing based on different technologies. These differ in the amount of information that is provided about your DNA.
The technology used by companies such as 23andMe or Ancestry are known as “microarrays” or simply “arrays”. These query hundreds of thousands of variants. Microarrays don’t examine all your DNA, all your genes, or even all known variants. The technology reports back on the variants that the company has chosen to test.
There are also services that will provide you with additional information if you upload the results from Ancestry or 23andMe. These services give you health information that 23andMe or Ancestry may not offer.
Understanding genetic risk
Some characteristics, particularly genetic disorders, can be caused by a single variant. That means a single change in our DNA can cause an effect. Cystic Fibrosis, some forms of color blindness, and some forms of cancer, are examples where a single variant in a single gene can cause a disease or a feature. If you recall Gregor Mendel and his famous peas, he examined whether they would be smooth vs wrinkled, or yellow vs green. These would also be examples of such features. These are known as monogenic traits, simple traits, or Mendelian traits.
However, for many of our features, there’s a multitude of factors that impact our risk in developing that characteristic and are known as complex traits. Examples include many types of cancer, type II diabetes, food metabolism, Alzheimer’s, and intelligence, among many others. For complex traits, there are many different genes which incrementally contribute towards our risk together with environmental factors. This is one of many reasons why it is difficult to develop drugs for complex traits as well: there’s no single reason or risk factor for it.
Genome-Wide Association Studies
When scientists examine complex traits, they have to look at very large sets of individuals. Using microarrays, they examine variants across the entire genome and see if there are any variants that are found more frequently in individuals that have the trait vs individuals that do not. These are called Genome-Wide Association Studies or GWAS. These studies have to be very well designed and properly analyzed, and should be reproduced in different populations to ensure that the variants identified were not due to random chance.
It’s important to know that the variants identified in GWAS are not necessarily what cause the trait. They’re merely associated with it.
When you receive the results for non-clinical genetic tests stating that you are more/less likely to have a given trait, it is important to check to see the strength of the evidence supporting the association. Is it just one paper examining a handful of individuals? Or have there been several papers examining hundreds/thousands of individuals?
At the same time, it is important to note the impact that the variant has on the trait. For example, have studies shown that the variant is associated with a 50% increased risk for developing colorectal cancer? Or does it increase your risk by 5%? Also, what is the base risk for the trait? For example, if you have a variant which doubles your risk for colorectal cancer, does it increase your risk from 1% to 2%? Or from 10% to 20%?
How accurate are direct-to-consumer genetic tests?
There are now a slew of tests that claim to predict for complex traits, such as what diet you should adhere to, whether your child will grow up to become an outstanding soccer player, and what kind of wine you should drink based on your DNA. Seldom is there strong evidence supporting these associations, and as previously noted, details on the strength of evidence/association is crucial yet is seldom provided. As such, results from non-clinical genetic tests should be treated with skepticism.
Because different companies examine and/or report on different variants, the results you get can also vary. In this report from statnews, for example, the journalist examined diet/fitness recommendations based on her DNA from a few different companies and the results varied greatly.
At the moment, the result of health data provided by non-clinical genetic tests are very unlikely to fully predict your risk for a complex trait. For example, if a genetic test tells you that you do not have a specific variant that is associated with Alzheimer’s, that does not mean that you will not develop Alzheimer’s. The result is specific to a single variant. There may be dozens more that are not tested for or have yet to be identified. As previously described, there are also environmental factors that are not accounted for.
Our understanding of complex traits and our risk associated with different variants is growing every day. But we’re far from being in a world where your future can be predicted from a cheek swab.
Genetic testing for vaccine reactions
There is a growing belief that certain genes can correctly predict whether your child will have a vaccine adverse reaction. One gene in particular, MTHFR, often comes up in these conversations. According to the NIH’s website, this gene encodes for a protein that is involved in the complex process of making the amino acid methionine. Patients that have a defective MTHFR enzyme can suffer from homocystinurea, whose symptoms include nearsightedness, “an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.” There is little to no evidence supporting the idea that genetic variants can predict vaccine reactions.
Considerations when getting genetic tests
In 2008, United States passed the Genetic Information Non-Discrimination Act (GINA) which “protects individuals from genetic discrimination in health insurance and employment”. However, as outlined in this article, life insurance, disability insurance, and long-term care insurance are not covered by GINA, so having information on your genetic risk may impact your coverage and/or premiums.
Genetic testing can also help uncover familial relationships, depending on the company that you choose for the testing. This means you can find distant relatives, which happened in my husband’s case. And although it’s rare, unexpected findings can also occur: finding half-siblings, discovering your biological parents aren’t who you thought they were, finding relatives from sperm/egg donations, and even discovering cases of incest.
Personally, I advocate for the use of non-clinical genetic testing services that have strong privacy and security measures. No: I don’t think that someone will take my DNA and make a clone of me in a distant future. But I don’t know what it might be used for, so I just prefer to keep my information private. Other scientists do not share my concern over privacy.
Should I have my child genetically tested?
I reached out to Laura Hercher, a genetic counselor and faculty member at the Joan H. Marks Graduate Program in Human Genetics. She highlighted that it can “be hard to generalize about what is or isn’t appropriate. Parents, of course, are the ultimate arbiters of what is best for their child.” She pointed out that it is necessary to think about the possible consequences when testing a minor, particularly since many of the tests being marketed oversell their features. She stressed that “testing may reveal unexpected or significant information. When testing has medical implications, many professionals who work with children encourage parents to avoid genetic testing of minors when testing will not alter medical care in the near term, leaving the child with the option to decide for him or herself as an adult.”
With all this information at hand, what should you do? One thing must be stressed: a genetic test recommended by your doctor or genetic counsellor is very different than a non-clinically validated genetic test that you order online. Genetic tests, when used properly, can give parents answers to their children’s conditions. In some cases, such as when there’s little/no information on family history, these tests can be very helpful to inform parents of genetic risks. But when it comes to ordering a non-clinical test for my child online, or uploading genetic data to a website for additional information, I’m of the opinion that this is not something I’d want to do, because there’s little to no action that I can take. The science still isn’t very strong for complex traits such as soccer skills, so there’s little value. And although it’s pretty cool to know whether my kid has variants that make cilantro taste like soap or if he has a greater likelihood of having blue eyes, I can just ask him if he likes guacamole (which he does) and look in his eyes (which are blue). Later in life, he can decide whether he wants to have his genetic data at hand, knowing that there may be an impact on his insurance policies as a consequence of that information.
Disclosure: Layla has previously worked at companies that develop the technologies used for genetic testing, and has been directly involved in developing technologies that could be used for genetic testing. Her opinion in this piece is hers alone and does not reflect those of former employers. At the time of writing this piece, she was not employed by any companies developing such technologies, nor did she own any stocks (outside of standard retirement portfolios) in these companies.