Researchers discover genetic changes that protect against liver disease

DANVILLE, Pa. – Using data from Geisinger’s MyCode Community Health Initiative, researchers have discovered genetic changes associated with protection against liver disease, including nonalcoholic steatohepatitis (NASH) and cirrhosis. The discovery was published this week in The New England Journal of Medicine.  

In the largest sequencing study to date on the genetic basis of liver health, scientists at Regeneron Genetics Center and Geisinger sequenced the exomes of more than 540,000 people across five ancestry groups and multiple cohorts, including MyCode and the UK Biobank. Analyzing this genetic data along with deidentified health records, researchers found that people with loss-of-function mutations in one of two copies of the CIDEB gene had an approximately 53% reduction in the risk of nonalcoholic liver disease and approximately 54% reduction in the risk of nonalcoholic cirrhosis. The study also found that CIDEB mutations had greater protective associations in people with obesity or Type 2 diabetes, who are traditionally at higher risk for NASH, compared to people without these conditions. 

“These relatively rare genetic variants found to be protective against liver disease may help guide treatment for a larger population with fatty liver disease, which is the leading indication for liver transplantation," said Christopher D. Still, D.O., director of Geisinger’s Obesity Institute and a co-author of the study. “This is another example of data from our MyCode Community Health Initiative contributing to discoveries with the potential to improve care.”

Since its inception in 2007, MyCode has enrolled more than 314,000 participants. With DNA sequencing and health data available on nearly 185,000 of these participants, MyCode is the largest healthcare system-based study of its kind. MyCode was one of the first programs to return clinically actionable results to patient-participants through its Genomic Screening and Counseling (GSC) Program, and to date, more than 3,600 participants at increased risk for potentially life-threatening conditions have received genomic risk results. 

In addition to this latest study, analysis of MyCode data has contributed to a number of groundbreaking discoveries, including a rare genetic variant that protects against obesity. Geisinger researchers have recently received several grants to study the impact of genomics on health, including a study of the genetics of cancer, improvements in the diagnosis of familial hypercholesterolemia, and development of a tool to diagnose genetic disorders in real time.

For more information about MyCode, visit geisinger.org/mycode.

About Geisinger
Geisinger is among the nation’s leading providers of value-based care, serving 1.2 million people in urban and rural communities across Pennsylvania. Founded in 1915 by philanthropist Abigail Geisinger, the non-profit system generates $10 billion in annual revenues across 134 care sites - including 10 hospital campuses, and Geisinger Health Plan, with 600,000 members in commercial and government plans. The Geisinger College of Health Sciences educates more than 5,000 medical professionals annually and conducts more than 1,400 clinical research studies. With 26,000 employees, including 1,600 employed physicians, Geisinger is among Pennsylvania’s largest employers with an estimated economic impact of $14 billion to the state’s economy. On March 31, 2024, Geisinger became the first member of Risant Health, a new nonprofit charitable organization created to expand and accelerate value-based care across the country.  Learn more at geisinger.org or connect with us on Facebook, Instagram, LinkedIn and X.