There is strong evidence for both genetic and environmental risk factors comprising the aetiology of multiple sclerosis (MS). While much progress has been made in recent years in identifying common genetic variants using genome-wide association studies, alternative approaches have remained relatively neglected. The prevalence of MS in Orkney and Shetland is among the highest in the world. Previous studies have suggested that a higher degree of parental relatedness in these isolated communities may contribute to the high rates of MS, indicating that recessive effects have an important role in MS aetiology. The Northern Isles Multiple Sclerosis (NIMS) study investigated the potential role of genome-wide homozygosity in MS risk by genotyping 88 MS patients, 89 controls matched by age, sex and ancestry, and a further 89 controls matched for sex and ancestry, but passed the majority of lifetime risk of developing MS (>70 years of age). Three participants were removed on the basis of pedigree-genomic anomalies (n=263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.