DR2/DQw1 inheritance and haplotype sharing in affected siblings from multiple sclerosis families

Although the human leukocyte antigen DR2/DQw1 allele has been associated with multiple sclerosis, studies of DR2/DQw1 inheritance in multiple sclerosis multiplex families have yielded conflicting results. We examined this question in 'high-incidence' families, defined as families with more than 50% of siblings affected. DR2/DQw1 allele frequencies were significantly increased, particularly in mothers and affected siblings (p <0.0001). The transmission of DR2/DQw1 from both parents was more frequent in affected offspring (p = 0.005). While evidence for segregation of disease with a particular parental allele was lacking in most families, the frequency of haplotype sharing was higher in affected sib pairs (p <0.01).