- Press Release Distribution

Genetic variation with MASLD reveals subtypes and potential therapeutic avenues

A study reveals genetic subtypes, biomarkers, gene and pathway targets for the development of new treatments for this liver disease

( An astounding 30% of Americans currently have metabolic dysfunction-associated steatotic liver disease, or MASLD, which is formerly known as nonalcoholic fatty liver disease, or NAFLD.

And many are unaware that they have it.

Over time, MASLD can lead to cirrhosis, liver failure and even liver cancer. The disease is also associated with and might be caused by factors that contribute to obesity, diabetes, high cholesterol and heart disease.

“Many people are not aware that MASLD can also be a sign of another condition, like diabetes or cardiovascular disease,” said Elizabeth Speliotes, M.D., Ph.D., M.P.H., gastroenterologist at Michigan Medicine and professor of internal medicine and computational medicine and bioinformatics at the University of Michigan Medical School.

“Whether an individual will eventually develop MASLD and if they do, whether they will go on to develop a more advanced liver disease or other metabolic disease is not known. Furthermore, because MASLD and these other metabolic diseases have multiple causes that we could not previously separate, current treatments are often imprecise, ineffective and/or riddled with many side effects.”

This is why Speliotes and a team of experts sought to identify the human genetic causes of MASLD.

“We wanted to better predict those individuals at highest risk for developing the disease, as well as provide direction for new therapeutics,” she said. 

Their findings were recently published in Nature Genetics.

Speliotes, who is the senior author of the study, and her team combined data across four multiethnic cohorts: the Genetics of Obesity-related Liver Disease, or GOLD, Consortium with CT-measured hepatic steatosis; U.K. Biobank participants with hepatic steatosis defined by MRI diagnosis code-defined cases of MASLD from the International Classification of Diseases, or ICD; the eMERGE database, which relies on electronic medical records to define MASLD cases and controls; and FinnGen, which includes ICD diagnosis code-defined cases of MASLD.

Their study involved 66,814 individuals with hepatic steatosis defined by imaging and 3,584 cases (versus 621,081 controls) of MASLD defined by diagnosis codes.

“It was important for us to examine data in many individuals, as we now had the power to diminish the noise and ultimately observe new and significant genetic associations,” said Nicholette Palmer, Ph.D., co-senior author of the study from Wake Forest University School of Medicine.

“It was also important for us to use new neural network modeling to quantitate liver fat in more than 40,000 MRIs in the U.K. Biobank,” said Yanhua Chen, Ph.D., an application programmer and senior analyst at Michigan Medicine and first author of the study.

“This provided us with high accuracy measurements in many MRIs where we previously did not have these measures. This increased our power to find reproducible hits.”

The team identified 17 genetic changes that contribute to MASLD, and by examining how these changes affected multiple human traits, the researchers were then able to identify seven subgroups of the disease.

According to Speliotes these genetic markers can now be used as biomarkers to identify disease subtypes and link them to tissues, genes and pathways that can be targeted to treat them.

“Effective treatments in MASLD are greatly needed and we hope our findings will help guide the development and targeting of the right treatment, for the right patient, at the right time,” said Michigan Medicine’s Xiaomeng Du, M.S., co-first author of the study.

“Further, the genetic markers combined with each other can identify 10%, 5% and 1% of the population at two-, three- and four-fold increased risk of developing advanced liver diseases like cirrhosis and hepatocellular carcinoma.”

Speliotes added that this is helpful because high-risk individuals are screened differently in hepatology when it comes to identifying and treating liver cancer early on, “when it is still curable.”

The team identified variation in liver lipid, cholesterol, steroid, alcohol and monocarboxylic acid processes as possibly disrupted in MASLD.

More specifically, they identified seven subclusters that affect lipid storage and release from hepatocytes, lipid recycling to the liver, peripheral adipose lipid storage and use, insulin signaling, intestinal absorption and glucose use (to make liver fat, break down fatty acids and/or enact the conversion of triglycerides and phospholipids.)

“Our research greatly increases our understanding of MASLD’s heterogenous causes,” said Speliotes. 

She also said that she hopes the team’s findings will lead to better care for MASLD patients by identifying high-risk individuals before the disease develops.

“If the disease does develop, getting the right treatment at the right time maximizes the effectiveness of the available treatments with far fewer debilitating side effects.”



Expert: The current pace of decarbonization in Massachusetts is too low to meet climate goals

Expert: The current pace of decarbonization in Massachusetts is too low to meet climate goals
Media contacts: Emily Gowdey-Backus, director of media relations, Nancy Cicco, assistant director of media relations,   Having worked with renewables for the last 15 years, and listening to the lofty goals political leaders make to achieve net-zero carbon emissions, UMass Lowell mechanical engineering Professor Christopher Niezrecki can tell you that as a state and a nation, we’re not on track. It’s not easy to wrap one’s head around the scale of the problem and even harder to come up with viable solutions. There is global scientific consensus that ...

Department of Energy announces $30 million for research to accelerate scientific advances at user facilities

WASHINGTON, D.C. - Today, the U.S. Department of Energy (DOE) announced $30 million in funding for three projects to increase scientific productivity and discoveries across DOE light source, neutron source, and high-performance computing and networking facilities. The DOE Office of Science provides researchers with access to the most advanced tools of modern science. The awarded projects are focused on developing the computational mathematics and scientific computing research needed to accelerate discovery and innovation at DOE’s X-ray and neutron source user facilities. “Scientific research is becoming ever more dependent on complex data ...

Internet-based therapy may help depression in people with multiple sclerosis

UNIVERSITY PARK, Pa. — Major depressive disorder affects up to 50% of all individuals with multiple sclerosis (MS) at some point during their lifetime and can lead to lower quality of life, greater disease progression and higher mortality. Patients enrolled in a phase 3 trial of an internet-delivered cognitive behavioral therapy program modified specifically for MS showed a large drop in depressive symptoms compared to a control group. The online program may offer an effective and easily accessible way to manage depression and lead to better quality of life for persons with ...

UNF receives substantial legislative funding to combat nursing shortage

UNF receives substantial legislative funding to combat nursing shortage
The University of North Florida has been awarded matching State legislative funding of nearly $800K based upon the School of Nursing's (SON) successful healthcare partnerships with Mayo Clinic, HCA Healthcare South Atlantic Division and Baptist Health.      The Florida legislative budget allowance and Linking Industry to Nursing Education (LINE) Fund is contributing to nursing program enhancements including growing scholarships for UNF nursing students, opening the UNF MedNexus Deerwood Simulation Center, developing cohorts of undergraduate nursing students in the UNF accelerated prelicensure program and enhancing the UNF-HCA Simulation Center experience.      This ...

NIH study identifies foods to help pregnant people optimize intake of key nutrients

NIH study identifies foods to help pregnant people optimize intake of key nutrients
Most pregnant people in the U.S. are at risk of not getting enough of six nutrients important to a healthy pregnancy—vitamin A, vitamin D, folate, calcium, iron, and omega-3 fatty acids—from foods alone. Yet finding a combination of foods and supplements that delivers the right amounts of these nutrients without exceeding calorie recommendations or safety limits can be challenging. In a new study published in The Journal of Nutrition, researchers from NIH’s Environmental influences on Child Health Outcomes (ECHO) Program wanted to find low-calorie, nutrient-rich foods that could boost nutrient intake, much like dietary supplements do. They calculated ...

Carnegie Mellon University launches WebAssembly Research Center

Carnegie Mellon University has launched the WebAssembly Research Center to harness the potential of the open-source platform. The internet isn't just the internet anymore. Increasingly, users turn to the web to stream videos, play games, shop, edit photos, collaborate with colleagues and more. Those users expect the internet to work seamlessly on everything from a computer to a smartphone. To make that happen means juggling code in different languages written for different platforms. WebAssembly (Wasm) was created to do just that. "Ultimately, all software could one day run on WebAssembly," said Ben Titzer, director ...

Racial discrimination among teens linked to unhealthy stress hormone levels

Audio Scientists already know that the stress caused by racial discrimination is related to a host of chronic health conditions, but less is known about which types of discrimination are most harmful.    To answer that question, researchers at the University of Michigan School of Kinesiology surveyed 100 adolescents aged 13-19, who had obesity or who were overweight, about their experiences with institutional, peer, educational and cumulative discrimination.    They measured their salivary cortisol ...

Psychological aspects of erectile dysfunction deserve more attention, health scientists say

Washington, DC (September 27, 2023) -- Personality traits and mental health problems are among the factors linked to erectile dysfunction (ED), a condition that affects up to 80% of men over the age of 60. But researchers often overlook these psychological causes and their treatments in favor of biological components of ED, according to a new article in Current Directions in Psychological Science.  In a review of existing research, Mark S. Allen, Alex M. Wood (Leeds Trinity University), and David Sheffield ...

Ochsner Health named to Newsweek’s America’s Greatest Workplaces for Parents and Families 2023

NEW ORLEANS– Ochsner Health was recently named one of the 2023 America’s Greatest Workplaces for Parents and Families by Newsweek and market-data research firm Plant-A Insights Group. A large-scale employer study based on over 224,000 company reviews aided in selecting 800 companies and organizations nationwide for the inaugural list. “It is an honor to be named among the greatest workplaces in the nation for parents and families. Our top priority at Ochsner is to put patients first, and we know employees are at their best when they have a healthy work-life balance directly correlating with the high-quality care offered to our patients ...

Your Zoom background might influence the first impression you make

Your Zoom background might influence the first impression you make
In a new study, participants tended to judge faces appearing against backgrounds featuring houseplants or bookcases as more trustworthy and competent than faces with a living space or a novelty image behind them. Gender and facial expression also appeared to influence judgments. Research led by Paddy Ross, Abi Cook  and Meg Thompson at Durham University, UK is publishing in the open-access journal PLOS ONE on September 27, 2023. Prior research has demonstrated that first impressions can make a real difference in people’s lives; for example, ...


ASH: Novel combination therapy significantly reduces spleen volume in patients with myelofibrosis

ASH: Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias

ASH: Targeted oral therapy reduced disease burden and improved symptoms for patients with rare blood disorder

New Sylvester cancer study provides insight into underlying gene mutations in myelodysplastic syndromes

First-in-human clinical trial of CAR T cell therapy with new binding mechanism shows promising early responses

Long-term results show combination treatment that skips chemotherapy is effective for older patients with Ph+ ALL

Mindfulness could help women with opioid use disorder better control drug urges

TTUHSC’s ARPA-H membership will spur innovation, improve access for West Texas patients

Global annual finance flows of $7 trillion fueling climate, biodiversity, and land degradation crises

Tracing how the infant brain responds to touch with near-infrared spectroscopy

These are the world's most effective charities

When is an aurora not an aurora?

Advisory panel issues field-defining recommendations for US government investments in particle physics research

Doctors discover many patients at UNC’s Inflammatory Bowel Disease Clinic screen positive for malnutrition

BNL: Advisory panel issues field-defining recommendations for U.S. government investments in particle physics research

International collaboration uses faculty member’s research on ancient Roman migration, seeks to understand Balkan genomic history

USF Health Heart Institute doctors are upbeat about cardiac regeneration

AI-driven breakthroughs in cells study: SFU-UBC collaboration introduces "MCS-detect" for advancements in super-resolution microscopy

Advisory panel issues field-defining recommendations for investments in particle physics research

$3.8 million NIH grant to fund Southwest Center on Resilience for Climate Change and Health

What happens when the brain loses a hub? 

Study reveals Zika’s shape-shifting machinery—and a possible vulnerability

RIT leading STEM co-mentoring network

Genetic mutations that promote reproduction tend to shorten human lifespan, study shows

CAMH develops potential new drug treatment for multiple sclerosis

Polyethylene waste could be a thing of the past

A dynamic picture of how we respond to high or low oxygen levels

University of Toronto researchers discover new lipid nanoparticle that shows muscle-specific mRNA delivery, reduces off-target effects.

Evolving insights in blood-based liquid biopsies for prostate cancer interrogation

Finding the most heat-resistant substances ever made

[] Genetic variation with MASLD reveals subtypes and potential therapeutic avenues
A study reveals genetic subtypes, biomarkers, gene and pathway targets for the development of new treatments for this liver disease