Skip to Main Content

An official website of the United States government

The impact of pregnancy history on genome-wide methylation patterns in women with and without multiple sclerosis

Principal Investigator
Name
Vilija Jokubaitis
Degrees
B. Com/B.Sci (Hons), PhD
Institution
Monash University
Position Title
Senior Research Fellow
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-789
Initial CDAS Request Approval
May 21, 2021
Title
The impact of pregnancy history on genome-wide methylation patterns in women with and without multiple sclerosis
Summary
Multiple sclerosis (MS) is a complex and multifaceted disease underpinned by autoimmunity-driven neuroinflammation and neurodegeneration. MS affects almost three million people globally, making it the leading cause of neurological disability in young people. Around 75% of people with MS are women; typically diagnosed in their prime reproductive years (20-40 years old). There is evidence that pregnancy is beneficial to women with multiple sclerosis (MS) by reducing disease progression and associated disability. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and central nervous system function.

DNA methylation is an epigenetic mechanism that regulates gene expression through the presence or absence of a CH3 (methyl) group on cytosine-phosphate-guanine (CpG) dinucleotides. Methylation age is a form of biological age predicted using methylation levels at a set of CpG sites, which differ between indices. There is evidence that methylation age higher than chronological age (known as methylation age acceleration, MAA) is an indicator of all-cause morbidity and mortality. Conversely, reduced MAA (i.e. methylation age deceleration) has been associated with female sex and a history of pregnancy.

The effect of pregnancy on the epigenome is understudied in all women. Understanding pregnancy-related methylation changes that are specific to women with MS may reveal the molecular mechanisms underpinning the long-term effect of pregnancy in women with MS. This may lead to the identification of novel therapeutic targets in the epigenome.
Aims

1. Identify associations between methylation patterns and parity in women with MS.
a. Identify associations between whole blood methylation patterns and parity.
b. Identify associations between immune cell subset methylation patterns and parity using statistical deconvolution methods.
c. Identify associations between MAA and parity using multiple methylation age indices (Horvath, Hannum, PhenoAge and GrimAge).

2. Identify associations between methylation patterns and parity in women without MS.
a. Identify associations between whole blood methylation patterns and parity.
b. Identify associations between immune cell subset methylation patterns and parity using statistical deconvolution methods.
c. Identify associations between MAA and parity using multiple methylation age indices (Horvath, Hannum, PhenoAge and GrimAge).

3. Compare findings from Aims 1 and 2 to identify pregnancy-related methylation changes that are specific to women with MS.

Collaborators

Alexandre Xavier; Centre for Information Based Medicine, Hunter Medical Research Institute
Jeannette Lechner-Scott; Centre for Information Based Medicine, Hunter Medical Research Institute, Department of Neurology, John Hunter Hospital
Helmut Butzkueven; Department of Neuroscience, Central Clinical School, Monash University, Department of Neurology, Alfred Health
Rodney J Scott; Centre for Information Based Medicine, Hunter Medical Research, School of Biomedical Sciences and Pharmacy, University of Newcastle, Division of Molecular Medicine, New South Wales Health Pathology North
Rodney A Lea; Centre for Information Based Medicine, Hunter Medical Research Institute, Institute of Health and Biomedical Innovation, Queensland University of Technology
Vilija Jokubaitis; Department of Neuroscience, Central Clinical School, Monash University, Department of Neurology, Alfred Health