DNA methylation linked to Crohn’s disease susceptibility, progression

LAS VEGAS — Dysregulated DNA methylation may contribute to susceptibility and progression of Crohn’s disease, according to new research presented at the Crohn’s & Colitis Congress.

Investigators concluded that these findings “may offer new pathophysiological insights and therapeutic targets to prevent the onset of [Crohn’s disease] and delay its progression.”

“It appears that most disease-associated methylation changes are triggered by the onset of Crohn’s disease,” Hari Somineni, a graduate student at Emory University and Children's Healthcare of Atlanta, said during his presentation. “We found that Crohn’s disease at diagnosis is associated with widespread changes in DNA methylation, which are predominantly consequences of the disease.”

Because accumulating evidence suggests gene-environment interactions may contribute to risk and progression in Crohn’s disease, Somineni and colleagues aimed to study the impact of DNA methylation in this disease.

To do so, they analyzed genome-wide DNA methylation data using blood DNA samples from 164 newly diagnosed children with Crohn’s disease who participated in the RISK study, as well as 74 controls. They noted that 54 of the Crohn’s patients showed disease progression within 36 months of their diagnosis.

Somineni and colleagues identified 1,043 CpGs that significantly correlated with susceptibility to Crohn’s disease (false discovery rate < .05). Among them, 849 were hypermethylated and 194 were hypomethylated in patients vs. controls.

Researchers found the CpGs with the strongest association to Crohn’s disease in a long non-coding RNA called LOC100996291.

They noted that 142 of the CpGs also correlated to Crohn’s disease progression, which suggests there are common epigenetic processes underlying both susceptibility and progression of the disease. They concluded that their findings show some of these CpGs may be causal rather than the consequence of Crohn’s disease, and may therefore represent new targets for treatment.

Another notable finding was the “methylomic reversion that is happening during the course of the disease,” Somineni told Healio Gastroenterology and Liver Disease by email. “Disrupted methylation patterns during diagnosis of [Crohn’s disease] revert back (except at the very few potentially causal CpGs), irrespective of disease behavior states (B1/B2), and it seems somehow related to the inflammatory status.”

He added that these findings are likely applicable to other autoimmune and inflammatory diseases, “and highlights how to appropriately design future studies of the role of epigenetic mechanisms in disease progression of complex traits.” – by Adam Leitenberger

Reference:

Somineni H, et al. Abstract 10. Presented at: Crohn’s & Colitis Congress; Jan. 19-20, 2018; Las Vegas, NV.

Disclosures: Somineni reports no relevant financial disclosures. Please see the full abstract for all other authors’ relevant financial disclosures.