Abstract
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.
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Acknowledgements
We would like to thank the people of Orkney and Shetland who kindly participated in this study. We are also grateful to Dr Sarah Taylor, Dr Marthinus Roos and the general practices of Orkney and Shetland, for assistance in recruiting participants; Kay Lindsay and Susan Hermiston, for project management and administration; Jo Graham, for meticulous work in tracing the pedigrees of study participants; Mirna Kirin, for invaluable statistical advice; Gisela Barr, for data entry, and Lesley McGoohan, for database work. DNA extraction was performed at the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, and genotyping was performed at GeneProbe (Tepnel), Livingston, West Lothian. This work was supported by the MS Society UK, the Volant Trust and Royal Society.
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McWhirter, R., McQuillan, R., Visser, E. et al. Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders. Eur J Hum Genet 20, 198–202 (2012). https://doi.org/10.1038/ejhg.2011.170
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DOI: https://doi.org/10.1038/ejhg.2011.170
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