Orkney and Shetland, the population isolates that make up the Northern Isles of Scotland, are of particular interest to multiple sclerosis (MS) research. While MS prevalence is high in Scotland, Orkney has the highest global prevalence, higher than more northerly Shetland. Many hypotheses for the excess of MS cases in Orkney have been investigated, including vitamin D deficiency and homozygosity: neither was found to cause the high prevalence of MS. It is possible that this excess prevalence may be explained through unique genetics. We used polygenic risk scores (PRS) to look at the contribution of common risk variants to MS. Analyses were conducted using ORCADES (97/2118 cases/controls), VIKING (15/2000 cases/controls) and Generation Scotland (30/8708 cases/controls) data sets. However, no evidence of a difference in MS-associated common variant frequencies was found between the three control populations, aside from HLA-DRB1*15:01 tag SNP rs9271069. This SNP had a significantly higher risk allele frequency in Orkney (0.23, p value = 8 × 10^–13) and Shetland (0.21, p value = 2.3 × 10^–6) than mainland Scotland (0.17). This difference in frequency is estimated to account for 6 (95% CI 3, 8) out of 150 observed excess cases per 100,000 individuals in Shetland and 9 (95% CI 8, 11) of the observed 257 excess cases per 100,000 individuals in Orkney, compared with mainland Scotland. Common variants therefore appear to account for little of the excess burden of MS in the Northern Isles of Scotland.

奥克尼群岛和设得兰群岛是构成苏格兰北部群岛的两个种群，对多发性硬化症 (MS) 研究特别感兴趣。虽然多发性硬化症在苏格兰的患病率很高，但奥克尼群岛的患病率是全球最高的，高于更北部的设得兰群岛。奥克尼群岛多发性硬化症病例过多的许多假设都已得到研究，包括维生素 D 缺乏和纯合性：均未发现导致多发性硬化症高患病率的原因。这种过度流行可能是通过独特的遗传学来解释的。我们使用多基因风险评分 (PRS) 来研究常见风险变异对 MS 的影响。使用 ORCADES（97/2118 例/对照）、VIKING（15/2000 例/对照）和 Generation Scotland（30/8708 例/对照）数据集进行分析。然而，除了HLA-DRB1*15:01标签 SNP rs9271069 之外，在三个对照群体之间没有发现 MS 相关常见变异频率存在差异的证据。该 SNP 在奥克尼群岛 (0.23， p值 = 8 × 10 ^–13 ) 和设得兰群岛 (0.21，p值 = 2.3 × 10 ^–6 )的风险等位基因频率显着高于苏格兰大陆 (0.17)。据估计，这种频率差异在设得兰群岛每 100,000 人观察到的 150 例过量病例中占 6 例 (95% CI 3, 8)，在奥克尼群岛每 100,000 人观察到的 257 例过量病例中占 9 例 (95% CI 8, 11) ，与苏格兰大陆相比。因此，常见变异似乎并不能解释苏格兰北部群岛多发性硬化症的过度负担。