["Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients' genotypic risk of developing MS.", "A transmission disequilibrium test (TDT) of the DRB1*-DQB1* haplotypes in 943 trio families, confirmed a higher than expected transmission rate (over-transmission) of the *13:03-*03:01 (OR\u200a=\u200a2.9, P\u200a=\u200a7.6×10(-3)), *04:05-*03:01 (OR\u200a=\u200a2.4, P\u200a=\u200a4.4×10(-6)) and *03:01-*02:01 (OR\u200a=\u200a2.1, P\u200a=\u200a1.0×10(-15)) haplotype. In contrast, the *16:01-*05:02 (OR\u200a=\u200a0.5, P\u200a=\u200a5.4×10(-11)) and the *15:02-*06:01 (OR\u200a=\u200a0.3, P\u200a=\u200a1.5×10(-3)) haplotypes exhibited a lower than expected transmission rate (under-transmission). The independence of the transmission of each positively and negatively associated haplotype was confirmed relative to all positively associated haplotypes, and to the negatively associated *16:01-*05:02 haplotype. In patients, carriage of two predisposing haplotypes, or of protective haplotypes, respectively increased or decreased the patient's risk of developing MS. The risk of MS followed a multiplicative model of genotypes, which was, in order of decreasing ORs: *04:05-*0301/*03:01-*02:01 (OR\u200a=\u200a4.5); *03:01-*02:01/*03:01-*02:01 (OR\u200a=\u200a4.1); and the *16:01-*05:02/*16:01-*0502 (OR\u200a=\u200a0.2) genotypes. Analysis of DRB1 and DQB1 protein chain residues showed that the Val/Gly residue at position 86 of the DRB1 chain was the only difference between the protective *16:01- *15:02 alleles and the predisposing *15:01 one. Similarly, the Ala/Val residue at position 38 of the DQB1 chain differentiated the positively associated *06:02 allele and the negatively associated *05:02, *06:01 alleles."] Do hLA-DRB1-DQB1 haplotypes confer susceptibility and resistance to multiple sclerosis in Sardinia?