A recent investigation reported, for the first time, an association between variants in the IFIH1-GCA-KCNH7 locus and multiple sclerosis (MS). We sought to replicate this genetic association in MS with a new independent MS cohort composed of French Caucasian MS trio families. The two most significant IFIH1 single nucleotide polymorphisms, rs1990760 and rs2068330, reported as involved in MS susceptibility, were genotyped in 591 French Caucasian MS trio families, and analyzed using the transmission/disequilibrium test. No association with MS was found (rs1990760, P=0.45 and rs2068330, P=0.27). Similarly, no significant association was detected after stratification for HLA-DRB1*1501 carriers. Reasons that may explain this discrepancy between the original report and our study are discussed.