Generally, people may share the same genetic risk
factors but their chances to develop a disease are increased by specific
Scientists at the Wayne State University School of Medicine's Center
for Molecular Medicine and Genetics have shown for the first time the
extent by which interactions between environmental exposures and genetic
variation across individuals have a significant impact on human traits
and diseases like diabetes, heart disease and obesity, strengthening the
case for precision medicine initiatives.
‘Interactions between environmental exposures and genetic variation across individuals have a significant impact on human traits and diseases, strengthening the case for precision medicine initiatives.’
The discovery is particularly important when considering
communities with different ancestries sharing the same risk environment
- the case for many urban communities, including Detroit, the
researchers said. Human environments are difficult to measure,
especially when trying to study these complex interactions.
the researchers explained, it is hard to quantify the amount of stress
in a person's life or the caffeine or vitamin content in their diets.
"Both genes and environmental conditions are major influences on
our health and who we are. For example, stress is a risk factor for
cardiovascular disease; however, the actual risk to have a heart attack
depends not only on the amount of stress in a person's life but also on
the specific DNA sequences - genetic variants - that he or she
inherited from their parents," said researcher Francesca Luca, who led the study with co-principal investigator Roger Pique-Regi.
"The interplay between genetic variants and environments during human
evolutionary history provided the driving force that shaped our genome.
Today, genetic adaptations that helped us in the past to better store
energy in fat, for example, can make us more likely to develop a disease
like diabetes or obesity."
Luca and Pique-Regi are assistant professors of molecular
medicine and genetics, and of obstetrics and gynecology, and have spent
three years working on the project with a dedicated team of
collaborators that included several WSU students and postdoctoral
fellows, including recent graduate Gregory Moyerbrailean,
graduate student Cynthia Kalita; postdoctoral fellow Allison Richards and third-year medical student Daniel Kurtz.
Studying the interaction between genetic variants and environment
is an incredibly complex problem to tackle at the organismal level. The
WSU-based team explored, at the molecular level, gene expression
changes across 250 different cellular environments, including caffeine,
vitamins, metal ions, hormones, contaminants and common drugs.
"Our cellular system simplifies the complexity of the
environment, and allows us to develop robust statistical tests to
identify 215 genes with an activity modulated by genetic variants that
interact with our controlled environmental perturbations," Luca said.
"Surprisingly, 50% of these interactions are in genes important
for human traits and diseases. For example, one of these interactions in
the GIPR gene suggests that caffeine intake in the presence of a
genetic protective factor may decrease the risk to develop obesity.
Similarly, low selenium intake, in the presence of a genetic risk factor
in the LAMP3 gene, may further increase the risk for Parkinson's
This is the first time that large-scale genomic experiments have
shown that an individual's personal environment and genetic makeup can
directly affect and influence their health.
The results of the project are presented in the open-access Genome Research
article "High-throughput allele-specific expression across 250 environmental conditions," published last month.
In addition to the Genome Research
publication, the researchers presented two talks on their work at October's American Society of Human Genetics in Vancouver.
The research team is now investigating the precise molecular
mechanisms of the interactions, exploring additional environmental
exposures - including the human microbiome - and performing similar
studies in a large number of individuals of African American origin to
explore a larger number of genetic variants.