Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum Mol Genet 2006;15:2813–2824. [PubMed: 16905561

Variation in major histocompatibility complex genes on chromosome 6p21.3, specifically the human leuko-cyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for multiple sclerosis (MS). Previous studies of DRB1 variation and both MS susceptibility and phenotypic expression have lacked statistical power to detect modest genotypic influences, and have demonstrated conflicting results. Results derived from analyses of 1339 MS families indicate DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was strongly associated in families (P 5 7.8 3 10231), and a dominant DRB1*15 dose effect was confirmed (OR 5 7.5, 95 % CI 5 4.4–13.0, P<0.0001). A modest dose effect was also detected for DRB1*03; however, in contrast to DRB1*15, this risk was recessive (OR 5 1.8, 95 % CI 5 1.1–2.9, P50.03). Strong evidence for under-transmission of DRB1*14 (P 5 5.7 3 1026) even afte