Genetic factors are critical in multiple sclerosis (MS), and it is conceivable that the pattern recognition receptors of the innate immune system are of pathogenic importance. We therefore developed two novel assays capable of analyzing 42 single-nucleotide polymorphisms in the human genes encoding TLR1-10, NOD1-2, DDX58, and IFIH1. Using these assays, we genotyped 963 MS patients and 960 controls, and analyzed for possible associations to MS diagnosis, clinical course, severity, and age at onset. Our results support previous findings of associations between the IFIH1-locus and MS (IFIH1-rs3747517 and IFIH1-rs1990760 trend test: P=0.002 and P=0.014, respectively).