It's hard to overstate how much recent advances in genetics have changed how we study disease. As Eric Lander, one of the leaders of the Human Genome Project, explained to the Atlantic, "We can finally pop the hood on the car and see what’s wrong." Before the Human Genome Project, our ability to compare the DNA of people afflicted by a disease with that of healthy people was extremely limited—in fact, we didn't even know how many genes we had. Now, we can find disease-causing mutations by scanning the genomes of thousands of subjects in a single study. Since most diseases are influenced by genetics to some degree, looking under the hood to directly identify the relevant bits of DNA is a powerful way to understand and—sooner or later—treat complex diseases like cancer, diabetes, autism, and schizophrenia.
But researchers aren't just popping the hood to study the role of genes in disease; they're also interested in the genetic underpinnings of nominally healthy people. Understanding how differences in our DNA influence the ways we differ from each other is a fundamental problem in human genetics. Yet, by looking under the hood to find these genetic differences we also risk opening a Pandora's box of uncomfortable truths and potentially dangerous misunderstandings. Nowhere is this more true than in studies that explore the genetics of one of our most socially important traits: intellectual ability. A recent, provocative study shows that such research has the potential to be helpful, by improving our ability to identify children who are likely to need extra support in school. But it can also, if not read carefully, distract us from important issues that have nothing to do with genetics.
For carriers of rare, large CNVs, the drop-out rate was substantially higher: Depending on the type of CNV, 29 to 47 percent of carriers failed to complete high school.
The study, published this month in JAMA by a team of researchers based at the University of Lausanne in Switzerland, focuses on the link between intellectual disability and a certain class of mutations that have been linked to psychiatric and cognitive disorders, such as autism, schizophrenia, and complex syndromes of developmental delay. These mutations are called "copy number variants," or CNVs. They are essentially giant mutations, big segments of DNA that are either deleted or repeated in extra copies in certain individuals. We all carry CNVs, and they are an important source of genetic differences between us. Many specific CNVs are quite common and thus clearly benign—if they weren't, they likely wouldn’t be so common. Other CNVs are linked with known diseases and disorders. And then there is the most mysterious class of CNVs, ones that are rare—which suggests they could be harmful—but not yet linked to known diseases. These mutations are rare in the sense that each particular one is not carried by very many people. But it turns out that there are many different rare mutations, and many people may have one. This leads to an important and possibly uncomfortable question: Could rare CNVs be affecting the health or cognitive functioning of large numbers of people?
To answer this question, the Swiss researchers turned to a large biobank in Estonia that contained the critical elements required for a genetic study: DNA samples, plus health and lifestyle information for 52,000 volunteers—nearly five percent of the Estonian adult population. The researchers randomly selected 8,000 nominally healthy biobank participants, and checked their DNA samples for CNVs. They then determined whether the carriers of rare, large CNVs show signs of general intellectual disability or limited educational attainment.
It turns out that many of them do. The researchers found two categories of people who appear to be affected by the CNV mutations detected in their study. First, a small number of people (56, less than one percent of the study subjects) carried mutations that are known to be pathological. These are people who slipped through the medical system’s cracks: They were suffering from a genetic disorder but didn't know it. When the researchers examined their health records, most had traits—such as psychiatric problems, learning disabilities, and irregular body dimensions—that were consistent with the known disorders associated with their particular CNVs.
In the second and more provocative category were people who carried rare, large CNVs that are not yet linked with any particular disease. More than 10 percent of the study population carried such a CNV, and these people were much more likely to have ended their formal education before finishing the Estonian equivalent of high school. Across the entire study population, 25 percent of the subjects (who were all adults) did not complete high school. For carriers of rare, large CNVs, the drop-out rate was substantially higher: Depending on the type of CNV, 29 to 47 percent of carriers failed to complete high school. This suggests that at least some carriers of rare CNVs suffer from some form of intellectual disability, though knowing exactly what kind would require more analysis. The researchers followed up these findings with smaller studies of British, Italian, and American subjects, and they found similar trends. All together, the potential toll of these CNVs appears to be large: The researchers concluded that "the quality of life for 1 of 40 people might be negatively affected by rare CNVs."
There are, of course, large caveats to keep in mind. Level of education is only a rough stand-in for more direct measures of intellectual function. To establish a strong link between any particular CNV and intellectual disability would require a more detailed look at the clinical features of the study subjects. Still, this study is significant because it suggests that many people suffer from genetically caused learning disorders and intellectual disabilities, but they are hard to identify because they don’t fit the standard genetic profile. If we learned how to identify them, these people could possibly be helped and given opportunities to achieve their full potential.
Despite the importance of studies like this one, the subject of links between genetics, intelligence, and academic success has a long history of dangerous misunderstandings and outright injustices. We need to be tremendously careful not to let genetics distract us from the enormous non-genetic factors that block people from living up to their potential. Socioeconomic inequality is a huge factor. In a report for the New York Times last month, Susan Dynarski, a professor of education at the University of Michigan, drew on data from a Department of Education study to show how dramatically a student's chances for graduation from college track with their family’s socioeconomic status. Talented high school students who received top scores on a standardized math test, but who came from low-income, low-education families, were about as likely to graduate from college as high-status students whose scores were in the bottom half. Clearly, this is not a matter of genetics. As Dynarski put it, "class trumps ability when it comes to college graduation." Genetics can’t be an excuse to ignore or accept social injustice.
Genetic research designed to understand how DNA contributes to our uniquely human cognitive abilities tackles an inherently interesting scientific question. Research like the JAMA study is also important because it demonstrates just how complex the genetic underpinnings of learning disabilities really are, and it suggests that many more people are likely suffering from a genetically caused intellectual disability than we might expect. However, while we need to understand how our genes work and how they can go wrong, the source of some social and educational problems won't be found under the hood.
Inside the Lab explores the promise and hype of genetics research and advancements in medicine.