Air pollution and other environmental factors have a greater impact on genes related to respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma than genetic ancestry, a new Canadian study shows.
The research, “Gene-by-environment interactions in urban populations modulate risk phenotypes,” was published in the journal Nature Communications.
Disease susceptibility is influenced by environmental exposure and genetic variability. Individuals with different genotypes (genetic backgrounds) may respond differently to the environment and generate a vast array of phenotypes, which are characteristics or traits of an individual resulting from the interaction of the person’s genotype with the environment. However, the contribution of gene-environment interactions to disease risk remains poorly understood.
Researchers selected 1,007 individuals from CARTaGENE, the Quebec arm of Canada’s precision medicine initiative called Canadian Partnership for Tomorrow Project (CPTP). The CPTP has data from more than 315,000 Canadians and includes over 700 variables, including environmental exposures and longitudinal health information to assess genetic and environmental factors leading to chronic disease.
Scientists conducted a large-scale analysis of environmental datasets, biological samples, and health questionnaires. The study was one of the largest ever to address the link between environmental factors and gene expression, the researchers observed.
They focused on participants from Montreal, Quebec City, and Saguenay. Subjects’ genetic, health, and disease information were correlated with environmental data — including air pollution, the area’s walkability, and access to food — to analyze the effect these factors have on gene expression.
The analysis enabled a deep genetic characterization of the participants.
“We were surprised to find that we were able to stratify genetic ancestry within Quebec, identifying individuals whose descendants were from Montreal versus Saguenay, for example,” Philip Awadalla, PhD, the study’s senior author, said in a press release.
“This helped us to show how most gene expression is not derived by ancestry, and that environmental exposures associated with living in a particular city or region are more impactful on gene expression associated with disease traits than heritable variation,” he added.
Specifically, the scientists observed that exposure to high levels of particulate matter and nitrous dioxide in Saguenay affected gene expression associated with respiratory function and oxygen pathways. This high exposure led to increased prevalence of respiratory diseases such as COPD and asthma.
The data also demonstrated that certain genetic variants determine how one’s gene expression responds to environmental stimuli.
“Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges,” the researchers wrote.
“Our study shows how one can use the large scope and scale of data in Canada’s largest health cohort to better understand how our genes interact with environmental exposures and shape individual health,” Awadalla said.
Reza Moridi, Ontario’s Minister of Research, Innovation and Science, said: “Today, with quantities of data never before available, we are able to make important discoveries that will help us fight and overcome disease.”