Sitting in my doctor’s examination room, I was surprised when she told me, “Genetics don’t really matter for chronic disease.” Rather, she continued, “A person’s lifestyle, what they eat, and how much they exercise, determine whether they get heart disease.”
As a researcher who studies the genetics of disease, I don’t fully disagree – lifestyle factors play a large role in determining who gets a disease and who doesn’t. But they are far from the entire story. Since scientists mapped out the human genome in 2003, researchers have learned that genetics also play a large role in a person’s disease risk.
Studies that focus on estimating disease heritability – that is, how much genetic differences explain differences in disease risk – usually attribute a substantial fraction of disease variation to genetics. Mutations across the entire genome seem to play a role in diseases such as Type 2 diabetes, which is about 17% heritable, and schizophrenia, which is about 80% heritable. In contrast to diseases such as Tay-Sachs or cystic fibrosis, where mutations in a single gene cause a disease, chronic diseases tend to be polygenic, meaning they’re influenced by multiple mutations at many genes across the whole genome.
Every complex disease has both genetic and environmental risk factors. Most researchers study these factors separately because of technical challenges and a lack of large, uniform datasets. Although some have devised techniques to overcome these challenges, they haven’t yet been applied to a comprehensive set of diseases and environmental exposures.
In our recently published research, my colleague Alkes Price and I developed tools to leverage newly available datasets to quantify the joint effects that genetic and environmental risk factors have on the biology underlying disease.
Aspirin, genetics and colon cancer
To illustrate the effect gene-environment interactions have on disease, let’s consider the example of aspirin use and colon cancer.
In 2001, researchers at the Fred Hutchinson Cancer Research Center were studying how regularly taking aspirin decreased the risk of colon cancer. They wondered whether genetic mutations that slowed down how quickly the body broke down aspirin – meaning aspirin levels in the body would stay high longer – might increase the drug’s protective effect against colon cancer. They were right: Only patients with slow aspirin metabolism had a decreased risk of colon cancer, indicating that the effectiveness of a drug can depend on a person’s genetics.
This raises the question of how genetics and different combinations of environmental exposures, such as the medications a patient is taking, can affect a person’s disease risk and how effective a treatment will be for them. How many cases of genetic variations directly influencing a drug’s effectiveness are there?
