ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

ABSTRACT

Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10–5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.

KEYWORDS:

• DNA methylation
• alcohol withdrawal syndrome
• seizures
• carbohydrate deficient transferrin

Acknowledgments

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would like to thank Drs. Steven R.H. Beach and Thad Abrams for their assistance in editing the manuscript.

Availability of data and materials

The data described herein are available upon reasonable request to Dr. Philibert and may be restricted to non-commercial uses.

Disclosure statement

Dr. Philibert is the Chief Executive Officer of Behavioral Diagnostics. The use of cg05575921 to assess smoking status is covered by existing and pending patents including US Patents 8,637,652 and 9,273,358. Similarly, the use of DNA methylation to assess alcohol is covered by existing and pending patents including European Union Patent 3,149,206. On behalf of Drs. Philibert and Andersen, Behavioral Diagnostics and the University of Iowa have filed an intellectual property claim on the use of DNA methylation to predict AWS and related phenomena.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2023.2298057

Additional information

Funding

This work was supported by: R43AA027197, R44AA022041, R21AA029435 and UM1TR004403.