Childhood trauma and genetics linked to increased obesity risk

Childhood trauma and genetics linked to increased obesity risk

HPN Renown and DRI Logos

March 9, 2022
RENO, NV

Childhood Trauma
Genetics
Obesity

Above: The logos for the Healthy Nevada Project, DRI, and Renown Health.

Credit: DRI.

Childhood trauma and genetics linked to increased obesity risk 

New study from the Healthy Nevada Project® shows strong influence of genes and environment on human health 
Front page screenshot of Healthy Nevada Project study

The full text of the study, The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI, is available from Frontiers in Genetics: https://www.frontiersin.org/articles/10.3389/fgene.2022.816660/full

Reno, Nev. (March 9, 2022)New research from the Healthy Nevada Project® found associations between genetics, obesity, and childhood trauma, linking social health determinants, genetics, and disease. The study, which was published this week in Frontiers in Genetics, found that participants with specific genetic traits and who experience childhood traumas are more likely to suffer from adult obesity.  

In 2016, DRI and Renown Health launched the Healthy Nevada Project®, the nation’s first community-based, population health study, which now has more than 60,000 participants. The project is a collaboration with personal genomics company, Helix, and combines genetic, environmental, social, and clinical data to address individual and community health needs with the goal of improving health across the state and the nation.  

The new study focuses on Adverse Childhood Experiences (ACEs), which are traumatic and unsafe events that children endure by the age of 18. Over 16,000 participants in the Healthy Nevada Project® answered a mental health survey, and more than 65 percent of these individuals self-reported at least one ACE occurrence. These 16,000 participants were cross-referenced with their genetic makeup, and clinical Body Mass Index (BMI) measures.  

According to the research team’s findings, study participants who had experienced one or more types of ACE were 1.5 times more likely to become obese adults. Participants who experienced four or more ACEs were more than twice as likely to become severely obese.    

“Our analysis showed a steady increase in BMI for each ACE a person experienced, which indicates a very strong and significant association between the number of adverse childhood experiences and adult obesity,” said lead author Karen Schlauch, Ph.D., of DRI. “More importantly, participants’ BMI reacted even more strongly to the occurrence of ACEs when paired with certain mutations in several genes, one of which is strongly associated with schizophrenia.” 

“We know that genetics affect disease in the Healthy Nevada Project® [https://pubmed.ncbi.nlm.nih.gov/31888951/], and now we are recognizing that ACEs also affect disease,” said Healthy Nevada Project® Principal Investigator Joseph Grzymski, Ph.D., of DRI and Renown Health. “Our new study shows that the combination of genes and environmental factors like ACEs, as well as many social determinants of health, can lead to more serious health outcomes than either variable alone. More broadly, this new work emphasizes how important it is for population genetic studies to consider the impact of social determinants on health outcomes.” 

The study team believes that it is important for clinical caregivers to understand the strong impact that negative childhood experiences such as ACEs can have on both child and adult health. The researchers hope the information from this study will encourage doctors and nurses to conduct simple screenings for ACEs and consider a patient’s social environment and history in combination with genetics when developing treatment plans for better patient health. 

According to the 2019 Youth Behavior Risk Survey (YRBS), 25.6 percent of Washoe County teenagers are overweight or obese. Obesity is a serious health concern for children and adolescents. According to the Centers for Disease Control and Prevention, obese children and adolescents are more likely to become obese as adults.   

“Obese and overweight children and adolescents are at risk for multiple health problems during their youth, which are likely to be more severe as adults,” said Max J. Coppes, MD, PhD, MBA, FAAP, Nell J Redfield Chair of Pediatrics at the University of Nevada Reno School of Medicine, Physician in Chief of Renown Children’s Hospital. “Obese and overweight youth are more likely to have risk factors associated with cardiovascular diseases, such as high blood pressure, high cholesterol, and type 2 diabetes. Losing weight, in addition to a healthy diet, helps to prevent and control multiple chronic diseases and improves quality of life for a lifetime.”  

“We’d like to thank all of the Healthy Nevada Project® participants who provided information to make our work possible,” said Robert Read, M.S., of DRI. “Our research illustrates that it’s not just genetics that cause disease, but that our environment and life experiences interact with our genes to impact our health in ways that we are only beginning to understand.” 

Many thanks to Renown Health, the Stacie Mathewson Behavioral Health and Addiction Institute, and the Center for Genomic Medicine at DRI for supporting this significant work. Renown is currently enrolling participants in the world’s largest community-based genetic population health study, the Healthy Nevada Project®. For more information, visit renown.org. 

More information: 

The full text of the study, The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI, is available from Frontiers in Genetics: https://www.frontiersin.org/articles/10.3389/fgene.2022.816660/full 

This project was funded by the Stacie Mathewson Behavioral Health and Addiction Institute, Renown Health, and the Renown Health Foundation. Study authors included Karen Schlauch (DRI), Robert Read (DRI), Iva Neveux (DRI), Bruce Lipp (DRI), Anthony Slonim (Renown Health), and Joseph Grzymski (DRI/Renown Health). 

For more information on the Healthy Nevada Project®, please visit: https://healthynv.org/ 

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About DRI

The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu.

About Renown 

Renown Health is the region’s largest, locally governed, not-for-profit integrated healthcare network serving Nevada, Lake Tahoe and northeast California. With a diverse workforce of more than 7,000 employees, Renown has fostered a longstanding culture of excellence, determination and innovation. The organization comprises a trauma center, two acute care hospitals, a children’s hospital, a rehabilitation hospital, a medical group and urgent care network, and the region’s largest, locally owned not-for-profit insurance company, Hometown Health. Renown is currently enrolling participants in the world’s largest community-based genetic population health study, the Healthy Nevada Project®. For more information, visit renown.org. 

Media contacts: 

Kelsey Fitzgerald, DRI
Senior Communications Official
775-741-0496
Kelsey.fitzgerald@dri.edu 

Renown Public Relations
775-691-7308
news@renown.org 

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

December 1, 2021
RENO, NEV.

By Kelsey Fitzgerald

Antarctic Sea Squirt
Melanoma
Health

Above: Late spring at Arthur Harbor. The waters surrounding Anvers Island, Antarctica, are home to a species of sea squirt called Synoicum adareanum. New research has traced the production of palmerolide A, a key compound with anti-melanoma properties, to a member of this sea squirt’s microbiome.

Credit: Alison E. Murray, DRI

New study brings important advances for Antarctic science and natural products chemistry

There are few places farther from your medicine cabinet than the tissues of an ascidian, or “sea squirt,” on the icy Antarctic sea floor – but this is precisely where scientists are looking to find a new treatment for melanoma, one of the most dangerous types of skin cancer.

In a new paper that was published today in mSphere, a research team from DRI, Los Alamos National Laboratory (LANL), and the University of South Florida (USF) made strides toward their goal, successfully tracing a naturally-produced melanoma-fighting compound called “palmerolide A” to its source: a microbe that resides within Synoicum adareanum, a species of ascidian common to the waters of Antarctica’s Anvers Island archipelago.

“We have long suspected that palmerolide A was produced by one of the many types of bacteria that live within this ascidian host species, S. adareanum,” explained lead author Alison Murray, Ph.D., research professor of biology at DRI. “Now, we have actually been able to identify the specific microbe that produces this compound, which is a huge step forward toward developing a naturally-derived treatment for melanoma.”

Synoicum adareanum

Synoicum adareanum in 80 feet of water at Bonaparte Point, Antarctica. New research has traced the production of palmerolide A, a key compound with anti-melanoma properties, to a suite of genes coded in the genome by a member of this sea squirt’s microbiome.

Credit: Bill J. Baker, University of South Florida.
Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with antimelanoma palmerolide biosynthetic potential

The full study, Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with anti-melanoma palmerolide biosynthetic potential, is available from mSphere: https://doi.org/10.1128/msphere.00759-21.

The bacterium that the team identified is a member of a new and previously unstudied genus, Candidatus Synoicihabitans palmerolidicus. This advance in knowledge builds on what Murray and her colleagues have learned across more than a decade of research on palmerolide A and its association with the microbiome (collective suite of microbes and their genomes) of the host ascidian, S. adareanum.

In 2008, Murray worked with Bill Baker, Ph.D., professor of chemistry at USF and Christian Riesenfeld, Ph.D., postdoctoral researcher at DRI to publish a study on the microbial diversity of a single S. adareanum organism. In 2020, the team expanded to include additional researchers from LANL, USF, and the Université de Nantes, and published new work identifying the “core microbiome” of S. adareanum – a common suite of 21 bacterial species that were present across 63 different samples of S. adareanum collected from around the Anvers Island archipelago.

In the team’s latest research, they looked more closely at the core microbiome members identified in their 2020 paper to determine which of the 21 types of bacteria were responsible for the production of palmerolide A. They conducted several rounds of environmental genome sequencing, followed by automated and manual assembly, gene mining, and phylogenomic analyses, which resulted in the identification of the biosynthetic gene cluster and palmerolide A-producing organism.

“This is the first time that we’ve matched an Antarctic natural product to the genetic machinery that is responsible for its biosynthesis,” Murray said. “As an anti-cancer therapeutic, we can’t just go to Antarctica and harvest these sea squirts en masse, but now that we understand the underlying genetic machinery, it opens the door for us to find a biotechnological solution to produce this compound.”

“Knowing the producer of palmerolide A enables cultivation, which will finally provide sufficient quantity of the compound for needed studies of its pharmacological properties,” added Baker.

 

A diver collects samples of Synoicum adareanum in support of a microbiome and biosynthetic gene cluster study. Palmer Station Antarctica, March 2011.

Credit: Bill Dent, University of South Florida.

Many additional questions remain, such as how S. adareanum and its palmerolide-producing symbiont are distributed across the landscape in Antarctic Oceans, or what role palmerolide A plays in the ecology of this species of ascidian.  Likewise, a detailed investigation into how the genes code for the enzymes that make palmerolide A is the subject of a new report soon to be published.

To survive in the harsh and unusual environment of the Antarctic sea floor, ascidians and other invertebrates such as sponges and corals have developed symbiotic relationships with diverse microbes that play a role in the production of features such as photoprotective pigments, bioluminescence, and chemical defense agents. The compounds produced by these microbes may have medicinal and biotechnological applications useful to humans in science, health and industry. Palmerolide A is one of many examples yet to be discovered.

“Throughout the course of disentangling the many genomic fragments of the various species in the microbiome, we discovered that this novel microbe’s genome appears to harbor multiple copies of the genes responsible for palmerolide production,” said Patrick Chain, Ph.D., senior scientist and Laboratory Fellow with LANL. “However the role of each copy, and regulation, for example, are unknown. This suggests palmerolide is likely quite important to the bacterium or the host, though we have yet to understand it’s biological or ecological role within this Antarctic setting.”

“This is a beautiful example of how nature is the best chemist out there,” Murray added. “The fact that microbes can make these bioactive and sometimes toxic compounds that can help the hosts to facilitate their survival is exemplary of the evolutionary intricacies found between hosts and their microbial partners and the chemical handshakes that are going on under our feet on all corners of the planet.”

Diver in the Antarctic Peninsula

Andrew Schilling (University of South Florida) dives in 100 feet of water at Cormorant Wall, Antarctica. Samples for microbiome characterization were collected by SCUBA divers working in the chilly subzero seas off Anvers Island, in the Antarctic Peninsula.

Credit: Bill J. Baker, University of South Florida. 

More information:

The full study, Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with antimelanoma palmerolide biosynthetic potential, is available from mSphere: https://doi.org/10.1128/msphere.00759-21.

Study authors included Alison Murray (DRI), Chein-Chi Lo (LANL), Hajnalka E. Daligault (LANL), Nicole E. Avalon (USF), Robert W. Read (DRI), Karen W. Davenport (LANL), Mary L. Higham (DRI), Yuliya Kunde (LANL), Armand E.K. Dichosa (LANL), Bill J. Baker (USF), and Patrick S.G. Chain (LANL).

This study was made possible with funding from the National Institutes of Health (CA205932), the National Science Foundation (OPP-0442857, ANT-0838776, and PLR-1341339), and DRI (Institute Project Assignment).

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About DRI

The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu. 

About The University of South Florida

The University of South Florida is a high-impact global research university dedicated to student success. Over the past 10 years, no other public university in the country has risen faster in U.S. News and World Report’s national university rankings than USF. Serving more than 50,000 students on campuses in Tampa, St. Petersburg and Sarasota-Manatee, USF is designated as a Preeminent State Research University by the Florida Board of Governors, placing it in the most elite category among the state’s 12 public universities. USF has earned widespread national recognition for its success graduating under-represented minority and limited-income students at rates equal to or higher than white and higher income students. USF is a member of the American Athletic Conference. Learn more at www.usf.edu.

About Los Alamos National Laboratory

Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is managed by Triad, a public service oriented, national security science organization equally owned by its three founding members: Battelle Memorial Institute (Battelle), the Texas A&M University System (TAMUS), and the Regents of the University of California (UC) for the Department of Energy’s National Nuclear Security Administration. Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.

 

Study provides new insight into how microbes process nitrogen

Study provides new insight into how microbes process nitrogen

Reno, Nev. (Feb. 19, 2019): Microbes play a key role in Earth’s nitrogen cycle, helping to transform nitrogen gas from the atmosphere back and forth into organic forms of nitrogen that can be used by plants and animals.

New research from the Desert Research Institute in Reno, Nev. provides new insight into how this process happens, through the examination of a unique species of microbe called Intrasporangium calvum that was found in a contaminated groundwater well at Oak Ridge National Laboratory Field Research Station in Tennessee.

The study, which published in Frontiers in Microbiology in January, examined the response of I. calvum to different concentrations of environmental resources and how those differences impacted the microbe’s nitrogen cycling ability. The study team also investigated the evolution of this microbe, the biochemistry behind the reactions, and how each of those factors interact with the environment.

Although most microbes perform just one step in the nitrogen cycle – converting nitrogen gas (N2) from the atmosphere to ammonia (NH3) in the soil, for example – the research team discovered that I. calvum could perform two types of reactions: respiratory ammonification and denitrification. Respiratory ammonification retains nitrogen in an ecosystem as ammonium in the soil or water, while denitrification sends nitrogen on a path back to the atmosphere as a gas.

“The microbe that we studied is unique because it can essentially ‘breathe’ in nitrogen and then send the nitrogen along one of two pathways, ‘exhaling’ either ammonium or nitrous oxide,” said David Vuono, Ph.D., postdoctoral researcher fellow with DRI’s Division of Earth and Ecosystem Sciences and Applied Innovation Center, and lead author of the new study. “This is kind of like humans breathing in oxygen and then having the ability to exhale either carbon dioxide or methane.”

Sample bottles of I. calvum are sterilized via flame in the Genomics Laboratory at DRi. February 2019. Credit: DRI.

With the ability to perform more than one type of reaction – either sending nitrogen back to the atmosphere or retaining it in the soil or water – Vuono and his team wondered what would trigger the microbe to select one pathway versus the other. Previous studies had concluded that the ratio of carbon (C) to nitrate (NO3) in the surrounding environment was the determining factor, but Vuono wondered if the story wasn’t actually more complex.

In this study, Vuono and his team looked beyond the C:NO3ratio to investigate the importance of the overall concentration of each nutrient. They tested the response of I. calvumunder conditions of both high and low resource availability, while keeping the ratio of C:NO3at a constant level.

According to their findings, it is the resource concentration, rather than the C:NO3ratio, that determines pathway selection. When grown under low carbon concentrations, the team found that these microbes were more likely to process nitrogen by ammonification; under high carbon concentrations, denitrification prevailed.

“As we learned, the concentration of nutrients available to these microbes is what determines where the nitrogen ends up, whether it takes a pathway back towards the atmosphere or returns to ammonium,” Vuono explained. “That is a really important distinction, because depending on the environment that you’re in, you may want to remove nitrogen or you may want to retain it.”

In a waterway, for example, high levels of nitrogen can cause algae blooms and dead zones; by creating conditions that favor denitrification, it is possible that microbes could be triggered to send nitrogen back to the atmosphere. In an agricultural field, on the other hand, nitrogen deficiencies in the soil can lead to poor plant growth; by creating conditions that would promote respiratory ammonification, microbes could be prompted to retain nitrogen in the soils, eliminating or lessening the need for chemical fertilizers.

David Vuono, Ph.D., prepares a sample of I. calvum for analysis in the Laboratory of Molecular Responses at DRI. February 2019. Credit: DRI.

This study was funded by the Nevada Governor’s Office of Economic Development (GOED), the Desert Research Institute postdoctoral research fellowship program, Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA), and Oak Ridge National Laboratory (US Department of Energy, Office of Science, Office of Biological and Environmental Research).

Other DRI scientists who contributed to this study included Robert Read, John A. Arnone III, Iva Neveux, Evan Loney, David Miceli, and Joseph Grzymski.

The full study, titled Resource Concentration Modulates the Fate of Dissimilated Nitrogen in a Dual-Pathway Actinobacterium, is available online from Frontiers in Microbiology (22 January 2019): https://doi.org/10.3389/fmicb.2019.00003