Risk alleles for multiple sclerosis in multiplex families

Area of Science:

• Genetics
• Neurology
• Immunology

Background:

• Multiple sclerosis (MS) is a complex neurological disorder with a known genetic component.
• Susceptibility loci for MS have been identified, but their role in familial aggregation requires further investigation.

Purpose of the Study:

• To test if non-major histocompatibility complex MS susceptibility loci are common to sporadic and multiplex cases.
• To determine if these loci have larger effects in multiplex families.
• To assess if the aggregation of susceptibility loci contributes to increased MS prevalence in multiplex families.

Main Methods:

• Genotyped 732 individuals from 43 multiplex families for 13 MS candidate genes using genome-wide association data.
• Conducted a case-control analysis and family-based pedigree disequilibrium association test using a control dataset of 182 healthy individuals.

Main Results:

• Identified effects of IL2RA and CD58 loci in multiplex families, consistent with sporadic MS.
• Observed a significant aggregate effect of risk genotypes at IL2RA, IL7R, EVI5, KIAA0350, and CD58 in affected individuals from multiplex families (p = 1 x 10(-22)).

Conclusions:

• Aggregate results in multiplex families show increased effect sizes compared to sporadic MS studies.
• Concentrations of susceptibility alleles at IL2RA, IL7R, EVI5, KIAA0350, and CD58 contribute to heightened MS prevalence in multiplex families.