Can we reimagine how we understand the origins of disease?
Exposome Perspectives Blog by Robert O. Wright, MD, MPH
Have you ever read an article that concludes that a disease is 80% genetic and 20% environmental? Let’s break down what that means. There are studies that examine disease risk in identical and fraternal twins. Identical twins have the exact same genes, and fraternal twins share an average of 50% of their genetics. By comparing the rates of a disease in both types of twin pairs, the relative contributions of genes and environment can be estimated. However, these studies don’t account for the fact that all twins have identical environments in pregnancy and very similar environments thereafter, so they are really a “guesstimate” of the genetic contribution.
Studies like these make good soundbites because they simple to understand. If I were to tell you that a heritability study showed that asthma is 82% genetic— it would be reasonable to think this meant that out of every 100 people with asthma, 82 of them got it because of their genes and 18 got it because of their environment. But it doesn’t mean that and that is not how people get asthma. In fact, there is no known “gene” or “cluster of genes” that by itself causes asthma. We also know numerous environmental factors (pollen, animal dander, air pollution, stress and many, many others) can trigger asthma.
Biology is far too complicated to be boiled down like this without losing a ton of meaning. We present heritability results as if genes and environment work in isolation from one another. Further, we too often use language that suggests they work against each other (i.e. nature versus nurture), because it simplifies the ideas, but by doing so we create false impressions. Genes and environment work hand in hand. How can anyone ever decide how much of a percentage to give out to each? It’s like deciding what percent of the Beatles success you would give to Ringo.
The Problem With “Nature vs Nurture”
So why do we even bother with heritability? The origin of this problem comes from that simple phrase we all learned in high school, ‘nature vs nurture’. We use it to convey the idea that both genetics (nature) and environment (nurture) play a role in our health. In theory that seems like a good communication strategy, except our language conveys a different message. The “vs” in nature vs nurture implies a contest—like a prize fight. Nature vs nurture was first coined in the mid-1800s by English statistician Francis Galton (interestingly, he was Charles Darwin’s cousin) while writing about the influence of genetics and environment on intelligence. This 19th century concept is badly outdated. ‘Nature vs nurture’ seems to make us pick a side—genetics or environment, when we now know that both interact to determine disease risk and overall health.
100% Genetic, 100% Environmental
Ken Rothman, a famous epidemiologist, once wrote “all diseases are 100% genetic and 100% environmental.” In other words, they are not fighting, they are working together and always do. Another way to illustrate his point is to break down the role of environment in a genetic disease. If Dr. Rothman is right, then environment must play a big role in genetic diseases.
Let’s start with phenylketonuria, or PKU, for short. It is a genetic disorder that arises from a mutation in the phenylalanine hydroxylase gene. If a person has two copies of the mutated gene, they cannot properly metabolize phenylalanine, an amino acid, after it is ingested. Toxic products of metabolism accumulate and can damage the developing brain. Untreated, PKU can lead to intellectual disability, seizures, and behavioral problems. However, the disease will not occur if a newborn baby is given an environmental intervention—a special low phenylalanine formula.
This means the contributing factors of PKU, a disease we think is 100% genetic, would have a very different gene-vs-environment division if we did a twin study of PKU and developmental delays. This is because we treated and prevented developmental delay through an environmental intervention that interacted with genetics. That alone tells us that heritability is not dependent solely on genetics, but is determined by interactions of genes and environment.
So next time you read about a study that breaks down a disease into percentages of genetic and environmental causes, remember: genes always operate by interacting with the world in which we live. Is there an example of even one gene whose activity isn’t ultimately influenced by interaction with something that we experienced, ingested, inhaled, or acquired, and then synthesized in some way inside our body?
I will end with a quote attributed to neuropsychologist Donald Hebb, who studied language acquisition and learning in children. When asked ‘Which contributes more to personality: nature or nurture?’ he answered ‘Which contributes more to the area of a rectangle, its length or its width?’