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Study Description

This is a multi-centre, case-controlled study to develop a dataset containing 1000 MS cases and 1000 matched controls and to associate DNA sequence (allelic) variations with MS phenotypes.

Study subjects were enrolled through a prospective effort initiated in 2003. Three MS clinical centres were involved in subject recruitment and biological specimen collection using identical inclusion/exclusion criteria, two in Europe (Vrije Universiteit Medical Center, Amsterdam; and University Hospital Basel) and one in the US (University of California San Francisco). This study recruited subjects of northern-European ancestry with a diagnosis of MS (McDonald et al., 2001), with dissemination in time and space. Patients with Clinically Isolated Syndromes (CIS) were also included if they fulfilled 3 of the 4 Barkhof criteria for dissemination in space as per application of the McDonald criteria (McDonald et al., 2001). While recruitment predominantly included subjects with a relapsing onset of MS, individuals with all clinical subtypes of the disease participated, including clinically isolated syndrome (CIS), relapsing remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS).

The control group consisted of unrelated individuals, primarily spouses/partners, friends, and other volunteers. Control subjects were of northern-European ancestry and matched as a group, proportionally with cases according to age (±5 years) and gender. A familial history or current diagnosis of MS as well as a relation to another case or control subject were considered exclusionary for this group.

Protocols were approved by the Committees on Human Research at all Institutions and informed consent was obtained from all participants prior to participation in the study.

Primary Study Objective:
To identify DNA sequence variations (genotype) and flanking sequences that are associated with clinical factors (phenotype) which differ between study subjects with and without MS.

Secondary Study Objectives:

  1. To develop a clinical dataset including quantitative measures of 1000 well-characterized cases with MS, and 1000 ethnically matched controls.
  2. To identify other genotype-phenotype associations in MS study subjects such as magnetic resonance imaging (MRI) measures of disease burden and/or severity.
  3. To identify or confirm candidate surrogate markers of neurodegeneration using a variety of techniques including biochemical assays, blood transcriptome analysis, plasma proteomics and MRI*.

Genotyping
Genotyping of the complete dataset was performed at the Illumina facilities using the Sentrix® HumanHap550 BeadChip.

*MRI results are not available on dbGaP.

  • Study Design:
    • Case-Control
  • Study Type:
    • Case-Control
  • dbGaP estimated ancestry using GRAF-pop
Authorized Access
Publicly Available Data (Public ftp)
Study Inclusion/Exclusion Criteria

Case Inclusion Criteria
An MS subject will be eligible for inclusion in this study only if all of the following criteria apply:

  • Written informed consent
  • Males or females, aged 18 to 70
  • Northern-European ancestry
  • A diagnosis of MS (McDonald et al., 2001), with dissemination in time and space. A small number of patients with CIS may also be included, if they fulfill 3 of the 4 Barkhof criteria for dissemination in space as per application of McDonald criteria (McDonald et al., 2001)
  • EDSS of between 0 and 7.5
  • Ability and willingness to come back to the center after 12 months for the second investigation
  • No relapse within the 4 weeks prior to screening

Case Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • Subjects participating in ongoing MS clinical trials with non-approved drugs
  • Subjects receiving corticosteroids within 4 weeks of screening for treatment of MS. If non-systemic steroids are being used for other chronic inflammatory conditions, subjects may be included at the discretion of the investigator.
  • Any condition which in the opinion of the investigator would render the patient unsuitable for a MRI
  • Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months
  • Any concurrent illness, disability or clinically significant abnormality (including laboratory tests) that may prevent the subject from safely completing the assessments required by the protocol

Control Inclusion Criteria
A control subject will be eligible for inclusion in this study only if all of the following criteria apply:

  • Males or females, aged 18 to 70 years at the time informed consent is signed
  • No history or family history of MS
  • Able and willing to sign an informed consent form
  • Northern-European ancestry

Control Exclusion Criteria
A control subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • Has a past history or current diagnosis of MS
  • Is related to a case or another control

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanHap550v1.1 555352 38431
Selected publications
Diseases/Traits Related to Study (MeSH terms)
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