Abstract Details

Title Epigenetic Age is Minimally Correlated with Leukocyte Telomere Length in Pediatric Onset Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P6 - Poster Session 6 (11:45 AM-12:45 PM)

Poster/Presentation
Number 1-005

Objective

To determine the correlation between epigenetic clocks and telomere length in pediatric-onset MS (POMS) participants and age-similar pediatric controls.

Background Age is the strongest factor determining disease expression in multiple sclerosis (MS). Biological aging markers may capture these effects better than birthdate age. We previously demonstrated biological age acceleration in POMS compared to controls with both epigenetic clocks and telomere length. It is unknown whether these biomarkers are reporting overlapping or distinct aging-related processes.

Design/Methods

We conducted a cross-sectional case control study leveraging DNA samples and clinical data from the US Network of Pediatric MS Centers. Methylation scores were processed using Illumina’s Infinium Methylation EPIC BeadChip. Age acceleration residuals were calculated based on published lifespan and healthspan epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge). Leukocyte telomere length (LTL), measured by real time qPCR, was expressed as a telomere to single copy gene ratio (T/S). We employed multivariable analysis of covariance to assess correlation between epigenetic clocks and LTL adjusting for chronological age, sex, race, ethnicity, tobacco exposure, socioeconomic status, and BMI. We used multiple imputation to account for missingness.

Results We analyzed 300 POMS cases (mean age 15.7 years, SD 2.6) and 200 age-matched pediatric controls (mean age 15.2 years, SD 3.3). There was moderate to strong correlation among the epigenetic clocks and minimal correlation between these clocks and LTL for the entire cohort (POMS and controls) – Horvath (rho=0.083), Hannum (rho=0.014), PhenoAge (rho=0.055), and GrimAge (rho=0.075). When analyzed separately, the POMS and control participants demonstrated similar minimal correlations between epigenetic clocks and LTL.

Conclusions Epigenetic age and leukocyte telomere length were minimally correlated in this sample, suggesting the measures capture different processes and should not be used in place of each other. Our results support the use of multiple biomarkers to capture the complexities of aging in MS.

Authors/Disclosures
Jennifer H. Yang, MD (Rady Childrens Hospital/UCSD) PRESENTER	Dr. Yang has received research support from Pediatric Epilepsy Research Foundation. Dr. Yang has received research support from NIH.
Jonathan Race	Jonathan Race has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Co-Diagnostics.
Paige Sumowski	Ms. Sumowski has nothing to disclose.
Kayla Jacques, MD	Dr. Jacques has nothing to disclose.
Soha Fardad	Miss Fardad has nothing to disclose.
Ashley Fair, MAS	Ms. Fair has nothing to disclose.
Allison Schuette	Allison Schuette has nothing to disclose.
Jue Lin, PhD	Dr. Lin has nothing to disclose.
Defne Yilmaz, MSc	The institution of Miss Yilmaz has received research support from National Institutes of Health.
Gregory S. Aaen, MD (Loma Linda University School of Medicine)	Dr. Aaen has nothing to disclose.
Aaron W. Abrams, MD (Cleveland Clinic Foundation)	Dr. Abrams has nothing to disclose.
Leslie A. Benson, MD (Children's Hospital Boston)	The institution of Dr. Benson has received research support from ROHHAD Fight, Inc. The institution of Dr. Benson has received research support from NIH. The institution of Dr. Benson has received research support from Roche/Genentech. Dr. Benson has received personal compensation in the range of $0-$499 for serving as a consultant with MA Department of public health. Dr. Benson has received personal compensation in the range of $10,000-$49,999 for serving as a consultant with National vaccine injury compensation program.
Theron C. Casper, PhD (University of Utah)	Dr. Casper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aperta Biosciences. The institution of Dr. Casper has received research support from NIH. The institution of Dr. Casper has received research support from The National Multiple Sclerosis Society. The institution of Dr. Casper has received research support from Roche. The institution of Dr. Casper has received research support from Biogen. The institution of Dr. Casper has received research support from UCB.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Mark Gorman, MD	The institution of Dr. Gorman has received research support from Pfizer. The institution of Dr. Gorman has received research support from Roche / Genetech .
Timothy E. Lotze, MD, FAAN (Texas Children's Hospital)	Dr. Lotze has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Department of Justice VICP. The institution of Dr. Lotze has received research support from NIH. The institution of Dr. Lotze has received research support from National MS Society. The institution of Dr. Lotze has received research support from Sarepta Therapeutics. The institution of Dr. Lotze has received research support from PTC THERAPEUTICS. The institution of Dr. Lotze has received research support from Avexis. Dr. Lotze has received publishing royalties from a publication relating to health care. Dr. Lotze has received publishing royalties from a publication relating to health care.
Lauren B. Krupp, MD, FAAN (NYU Langone Medical Center)	Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EBIX. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman LaRoche. Dr. krupp has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MMMK. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Patrick, Dolan, and Kaufman. Dr. krupp has received intellectual property interests from a discovery or technology relating to health care.
Soe S. Mar, MD, FAAN (Washington University School of Medicine)	The institution of Dr. Mar has received research support from NIH.
Jayne Ness, MD (UAB Dept of Pediatrics, Div Pediatric Neurology)	An immediate family member of Dr. Ness has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jan One. The institution of Dr. Ness has received research support from Chugai/Roche. The institution of Dr. Ness has received research support from National Multiple Sclerosis Society. The institution of an immediate family member of Dr. Ness has received research support from NIH. An immediate family member of Dr. Ness has received publishing royalties from a publication relating to health care.
Mary R. Rensel, MD, FAAN	Dr. Rensel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for genentech. Dr. Rensel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG. Dr. Rensel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Rensel has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for TG. Dr. Rensel has stock in Brain Fresh LLC . The institution of Dr. Rensel has received research support from NMSS. The institution of Dr. Rensel has received research support from Roche- Genentech . The institution of Dr. Rensel has received research support from Biogen.
John W. Rose, MD, FAAN (Imaging and Neurosciences Center)	The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care.
Teri Schreiner, MD, MPH, FAAN (University of Colorado/ Children's Hospital of Colorado)	The institution of Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CDC. Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Schreiner has received research support from Roche Genentech.
Jan-Mendelt Tillema, MD (Mayo Clinic)	Dr. Tillema has nothing to disclose.
Amy T. Waldman, MD (Children's Hospital of Philadelphia)	Dr. Waldman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio. An immediate family member of Dr. Waldman has or had stock in Pfizer. The institution of Dr. Waldman has received research support from Ionis Pharmaceuticals. The institution of Dr. Waldman has received research support from Roche/Genentech. The institution of Dr. Waldman has received research support from Ionis Pharmaceuticals. The institution of Dr. Waldman has received research support from Calico. Dr. Waldman has received publishing royalties from a publication relating to health care. Dr. Waldman has received publishing royalties from a publication relating to health care.
Yolanda Wheeler	Yolanda Wheeler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Can Do MS. Yolanda Wheeler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Multiple Sclerosis Association . Yolanda Wheeler has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Multiple Sclerosis Association . Yolanda Wheeler has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Multiple Sclerosis Association . The institution of Yolanda Wheeler has received research support from National MS Society.
Lisa F. Barcellos, PhD (University of California, Berkeley)	No disclosure on file
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center)	The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.
Jennifer Graves, MD, PhD (UCSD)	Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Graves has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MSJ. The institution of Dr. Graves has received research support from Octave. The institution of Dr. Graves has received research support from Sanofi. The institution of Dr. Graves has received research support from EMD Serono.

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