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Updated: Jul 10, 2026
05:53
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
A genome-wide scan in forty large pedigrees with multiple sclerosis
Cristen J Willer1,2, David A Dyment1, Stacey Cherny1
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Journal of Human Genetics
|November 15, 2007
Summary
Genetic factors influence multiple sclerosis (MS) susceptibility. Despite identifying HLA DRB1*15 linkage in affected families, genome scans failed to confirm significant linkage, suggesting alternative genetic analysis methods may be needed for MS inheritance.
Area of Science:
- Genetics
- Neuroimmunology
- Epidemiology
Background:
- Multiple sclerosis (MS) susceptibility arises from complex gene-environment interactions.
- Identifying families with strong genetic effects can help reduce heterogeneity in MS genetic studies.
Purpose of the Study:
- To investigate genetic factors contributing to multiple sclerosis (MS) susceptibility in families with multiple affected individuals.
- To identify specific genetic markers or regions linked to MS inheritance.
Main Methods:
- Screened 18,794 probands to identify 40 families with four or more MS-affected individuals.
- Performed genome-wide scans and linkage analysis using parametric models with heterogeneity.
- Conducted transmission disequilibrium tests (TDT) and fine-mapping with microsatellite markers.
Main Results:
- HLA DRB1*15 was significantly associated with MS, present in 70% of affected individuals.
- Initial genome scan showed no significant linkage (HLOD > 3.3).
- Follow-up analysis identified a suggestive linkage (HLOD = 3.99) at marker D4S1597, but TDT did not confirm transmission distortion in this region.
Conclusions:
- While HLA DRB1*15 is associated with MS, significant linkage was not consistently found in highly multiplex families.
- Genome-wide linkage analysis may not be the optimal approach for dissecting MS inheritance in all genetic contexts.
- Further research may require alternative genetic dissection strategies for complex diseases like MS.
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