Researchers at Virginia Tech and the Mayo Clinic identified five distinct subgroups of metabolic dysfunction-associated steatotic liver disease, Nature Communications reported on September 2, 2026.
The investigators applied latent class analysis to clinical variables drawn from electronic health record data. Genetic variant evaluations and polygenic risk scores revealed that genetic factors contributed to disease profiles across all five groups. An independent patient cohort subsequently verified the classifications.
Patients grouped under the C2 and C3 classifications demonstrated high rates of type 2 diabetes, obesity, and sleep apnea. The C2 category represented a male-predominant cardiorenal subtype. The C3 group comprised a female-predominant cohort dealing with obesity and mood disorders, with patients showing relatively high use of antidepressant medication.
The C4 polygenic subgroup displayed the lowest incidence of metabolic comorbidities and ischemic heart disease. Patients in C4 experienced the highest overall rate of liver transplants. The authors reported that this transplant rate was likely driven in part by combinatorial genetic effects, linking high-prevalence risk alleles in TM6SF2 and MBOAT7 with a low prevalence of the protective HSD17B13 allele. Meanwhile, patients placed in the C5 polygenic subgroup showed an elevated risk of developing advanced fibrosis and acute renal failure.
Regeneron Genetics Center provided genetic data for participants in the Mayo Clinic Biobank. The Mayo Clinic Center for Individualized Medicine supported the biobank work alongside the Tapestry Study cohort, with additional funding provided to Shulan Tian by the Mayo Clinic Nutrition Obesity Research Program.
