WSU researchers show genetic variants and environmental exposures have influence on health

November 03, 2016

DETROIT - 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.

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. Generally, people may share the same genetic risk factors but their chances to develop a disease are increased by specific environmental exposures. Human environments are difficult to measure, especially when trying to study these complex interactions. For example, 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, Ph.D., who led the study with co-principal investigator Roger Pique-Regi, Ph.D. "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, Ph.D.; graduate student Cynthia Kalita; postdoctoral fellow Allison Richards, Ph.D.; 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 percent 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 disease."

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.
The work was supported by grants from the National Institutes of Health (R01 GM109215) and the American Heart Association.

About Wayne State University School of Medicine

Founded in 1868, the Wayne State University School of Medicine educates more than 1,000 medical students in all four classes. In addition to undergraduate medical education, the school offers master's degree, Ph.D. and M.D./Ph.D. programs in 14 areas of basic science to about 400 students annually.

Wayne State University is a premier urban research institution offering more than 380 academic programs through 13 schools and colleges to more than 27,000 students.

Wayne State University - Office of the Vice President for Research

Related Obesity Articles from Brightsurf:

11 years of data add to the evidence for using testosterone therapy to treat obesity, including as an alternative to obesity surgery
New research covering 11 years of data presented at this year's European and International Congress on Obesity (ECOICO 2020) show that, in obese men suffering from hypogonadism (low testosterone), treatment with testosterone injections lowers their weight and improves a wide range of other metabolic parameters.

Overlap between immunology of COVID-19 and obesity could explain the increased risk of death in people living with obesity, and also older patients
Data presented in a special COVID-19 session at the European and International Congress on Obesity (ECOICO 2020) suggests that there are overlaps between the immunological disturbances found in both COVID-19 disease and patients with obesity, which could explain the increased disease severity and mortality risk faced by obese patients, and also elderly patients, who are infected by the SARS-CoV-2 virus that causes COVID-19 disease.

New obesity guideline: Address root causes as foundation of obesity management
besity management should focus on outcomes that patients consider to be important, not weight loss alone, and include a holistic approach that addresses the root causes of obesity, according to a new clinical practice guideline published in CMAJ (Canadian Medical Association Journal)

Changing the debate around obesity
The UK's National Health Service (NHS) needs to do more to address the ingrained stigma and discrimination faced by people with obesity, says a leading health psychologist.

Study links longer exposure to obesity and earlier development of obesity to increased risk of type 2 diabetes
Cumulative exposure to obesity could be at least as important as actually being obese in terms of risk of developing type 2 diabetes (T2D), concludes new research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

How much do obesity and addictions overlap?
A large analysis of personality studies has found that people with obesity behave somewhat like people with addictions to alcohol or drugs.

Should obesity be recognized as a disease?
With obesity now affecting almost a third (29%) of the population in England, and expected to rise to 35% by 2030, should we now recognize it as a disease?

Is obesity associated with risk of pediatric MS?
A single-center study of 453 children in Germany with multiple sclerosis (MS) investigated the association of obesity with pediatric MS risk and with the response of first-line therapy in children with MS.

Women with obesity prior to conception are more likely to have children with obesity
A systematic review and meta-analysis identified significantly increased odds of child obesity when mothers have obesity before conception, according to a study published June 11, 2019 in the open-access journal PLOS Medicine by Nicola Heslehurst of Newcastle University in the UK, and colleagues.

Obesity medicine association announces major updates to its adult obesity algorithm
The Obesity Medicine Association (OMA) announced the immediate availability of the 2019 OMA Adult Obesity Algorithm, with new information for clinicians including the relationship between Obesity and Cardiovascular Disease, Diabetes Mellitus, Dyslipidemia, and Cancer; information on investigational Anti-Obesity Pharmacotherapy; treatments for Lipodystrophy; and Pharmacokinetics and Obesity.

Read More: Obesity News and Obesity Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to