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. 2001 Oct;69(4):900-3.
doi: 10.1086/323480. Epub 2001 Aug 22.

Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis

A Ligers  1 , D A Dyment, C J Willer, A D Sadovnick, G Ebers, N Risch, J Hillert; Canadian Collaborative Study Groups
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Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis

A Ligers et al. Am J Hum Genet. 2001 Oct.

Abstract

The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/disequilibrium test (chi2=138.3; P<.0001). We obtained significant evidence of linkage throughout the whole data set (mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (mlod=1.56; 62.7% sharing; P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.

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References

Electronic-Database Information

    1. ASPEX Package, The: Affected Sib-Pair Exclusion Mapping, ftp://lahmed.stanford.edu/pub/aspex/doc/usage.html (for the programs of Hinds and Risch's ASPEX-2.3 statistical package)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for MS [MIM 142860])

References

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