Not everything is genetic!

That genetic test may or may not tell you what you want to hearbut the answer is  probably a lot more complicated than the marketing suggests.

Last week, one genetic counselor, Katie Stoll, published her experiment with a direct-to-consumer testing company on a genetic counseling blog. 

The company ORIG3N peddles a Child Development DNA test. Katie submitted a cheek swab sample that was actually from her dog—and received back a test report. Then she submitted a cheek swab sample that just had tap water on it—and again received back a completed test report. 

ORIG3N has CLIA certification, which is supposed to provide regulatory oversight related to the analytical accuracy of testing. Obviously, at least in this specific case, CLIA certification did not ensure any level of analytical accuracy. Analytical and interpretive accuracy are both concerns with genetic testing, particularly with direct-to-consumer genetic testing. But what if the lab actually had run a test and accurately identified certain genetic variants: Would the results have been meaningful? 

The idea that a company would take a consumer’s $99 and spit out a nonsense report is troubling, but more troubling still is that the company is targeting parents, encouraging genetic testing of children, and suggesting that the results of genetic testing can predict a child’s “natural abilities for language and learning.” The company claims that their tests are based on “established scientific and medical research.” I took a quick look at the genes listed under the “Enlightenment” category of the so-called Child Development test.

“’There’s no such thing as the ‘gene for language.'”

It was easy to quickly find solid references related to the FOXP2 gene, next to which the company has indicated “language ability.” Thirty seconds of searching led to the Twitter feed for Dr. Simon E. Fisher, a scientist and linguist who has researched and published on the FOXP2 gene. The day after Katie’s post, in a nine-part tweet, he laments just these types of claims:

There’s no such thing as a “gene for language”. A Tweetorial to help explain why. In one branch of human genetics we search for correlations between particular gene variants that people carry and variations in an observed trait (normal variability and/or pathology)…1/9 “A gene for X” has become convenient shorthand to talk about associations between variation at these distant levels (genes & traits). This fuels a popular misconception of genes as abstract entities that can directly specify traits, including key aspects of human behaviour…2/9 What do genes really do? Many carry info for building proteins – strings of amino acids that fold into specific 3D structures with distinct jobs. Your genome has >20,000 such genes, encoding the molecular machinery of a cell (enzymes, signals/receptors, transporters, etc)…3/9 A brain is built via diverse cellular mechanisms. Precursors of neurons divide & proliferate, move to their final locations, become specialized, with outgrowths (dendrites/axons) that connect to other neurons. All these processes rely on networks of proteins working together..4/9 Learning = strengthening/weakening of connections in relevant brain circuits. Genes & proteins play crucial roles in those processes too. BUT there’s no 1-to-1 mapping between a single gene & any specific neural circuit. Mappings from circuits to behaviour are also complex…5/9 An example. We found that people with rare mutations of the FOXP2 gene have speech & language deficits, while general cognition is less affected. It’s frustrating how often FOXP2 is dubbed the “gene for language”, despite us emphasizing how misleading this framing can be…6/9 FOXP2 encodes a protein that switches on/off many other genes, not just in brain, also some non-neural tissues (e.g. lung, gut, heart). It’s not exclusive to humans, but has an evolutionary history spanning hundreds of millions of years. We see it in rodents, birds, fish etc..7/9 A few subtle, potentially interesting, changes to FOXP2 sequence arose on our lineage. But contributions of this gene to human traits are built on functions that are evolutionarily ancient. Experimental data suggest complex effects on neural connectivity & plasticity…8/9 FOXP2 is not here specially to bestow you with the gift of the gab. It has multiple roles in diverse tissues, across many species. Mutations have disproportionate effects on speech & language; asking how/why gives useful insights. Nuance is crucial, no language genes required.9/9

Genetic factors can be just as complex as environmental factors 

Genetics, environment, and chance all contribute to health conditions as well as to language development and athletic abilities… and the list goes on. It’s intuitive to most of us that environmental factors can be very complicated; some environmental factors we have control over and others we don’t. As Dr. Fisher so eloquently explains above, contributing genetic factors can be just as complex.

Polygenic is the norm—not the exception. 

Many direct-to-consumer tests are based at least in part on insight gleaned from GWAS studies. Knowing that a certain genetic “marker” or SNP is even slightly more common in a group of individuals who have a given health condition than in a group of individuals who do not have a given health condition is interesting from a research perspective—but it does not a clinically validated test make. There are a few clinically validated SNP-based tests newly being offered by medical genetic testing laboratories. These tests are not yet part of any medical society guidelines. SNP-based tests to guide medical management may be part of the future of medicine—but we’re not there yet.  

Remember the punnet squares from high school biology? I remember doing them with B.b. for brown eyes (dominant) and blue eyes (recessive trait). Ironically, even eye color is a complex trait that involves a number of different genes. Michael Dougherty, the former Director of Education for the American Society of Human Genetics proposed that we should change the way genetics is taught in school, to emphasize that most traits are in fact polygenic (influenced by a number of different genes). 

When and how is genetic testing actually valuable? 

There are many genetic conditions that fit into what are commonly (if also over simplistically) known as “single gene disorders” and further divided (again, with over-simplification) into “recessive” and “dominant” conditions: Cystic Fibrosis and Sickle Cell Disease are two common recessive conditions that are part of routine prenatal screening as well as Newborn Screening. Accurate diagnoses of these conditions can have a meaningful impact on treatment options and health outcomes and can also be important for family planning considerations. Hereditary cancer syndromes are most often inherited in a dominant pattern. Identifying a hereditary cancer mutation in a family can be valuable for knowing which family members are at increased risk for which cancers—beyond what might be suggested by looking at family history alone

Goals of the CDC’s Office of Public Health Genomics (OPHG) include appropriate testing for three common single gene disorders: Hereditary Breast/Ovarian Cancer Syndrome, Lynch Syndrome, and Familial Hypercholesterolemia. (Common in genetics still means that <1% of individuals have these conditions!) Other genetic testing that has the potential to guide medical management is often addressed in major societal guidelines. None of these are new. We’ve just done a poor job of implementing the genetics knowledge we already have about these common single gene disorders. 

Genetics + Environment + Chance 

Environmental factors also play a huge role. Diet and exercise are not as exciting to talk about as genetics, but they matter as much or more than genetics to health outcomes for the majority of individuals. Child development, including language development, is also shaped by environment and opportunities.As Dr. Ronald Bayer wrote several years ago, in response to the buzz over Precision Medicine: at a public health level, health inequalities have their roots in social and economic inequalities. As Rachel Adams wrote more recently, “While Precision Medicine is hardly eugenics, it does (at least in expenditure of research dollars) emphasize genes over the social determinants of health.”

Random chance also plays a real role in which of us develops which disease and when. And in child development. But you won’t find that in any marketing materials for genetic testing.

For Patients

  • If the marketing claims for a genetic test you’re considering sound too good to be true… that may be exactly the case.
  • Where is the lab’s evidence? The onus should be on the company offering testing to show the evidence behind the test they’re offering. Vague references to peer-reviewed literature or highlights or how many genes or “genetic markers” a company tests should not inspire confidence.
  • Ask a genetic counselor. Grey Genetics offers free 10-minute consults

For Healthcare Providers

  • There are a lot of high quality genetic testing options out there that can have a real impact on your patients’ medical management. There is also a lot of snake oil. Effective sales and marketing in this under-regulated field can make it difficult to tell the difference.
  • Look to your professional societal guidelines and what they say about genetic testing. The genetic testing options that are medically meaningful are often part of guidelines.
  • Speak with a genetic counselor. Grey Genetics is working on genetics support packages for healthcare providers. In the meantime, feel free to email me with questions or to schedule a free 10-minute consultation.  If you have a genetic counselor within your hospital or medical practice, reach out to them to talk about testing options, when and how you refer patients, and how you can work together better.
References & Further Reading:

Stoll, Katie. “DTC: Direct to Children?” The DNA Exchange. May 10, 2018.

Rogers P, Capitanini L, Copenhagen C. “Home DNA Kits: What Do They Tell You?” NBC 5 Chicago.  

Hercher, Laura, “Genome Culture: A Personal Risk Score May Be the Next Big Thing in Medicine.Genome. April 27, 2018. 

Dougherty, Michael J. “Closing the Gap: Inverting the Genetics Curriculum to Ensure an Informed Public.” Commentary. The American Journal of Human Genetics 85, 6–12, July 10, 2009

Bayer R, Galea S. “Public Health in the Precision-Medicine Era.” N Engl J Med 2015; 373:499-501.

Adams, Rachel. “Book + Worm: On Genes, Equality, and Social Justice.” Medium. April 7, 2018.

How Not To Talk About Race and Genetics.” Buzz Feed. March 30, 2018.

Do you meet genetic testing criteria for hereditary breast cancer risk?