Center of Health Science, University of the Faroe Islands, Tórshavn, Faroe Islands.
Department of Occupational Medicine and Public Health, Faroese Hospital System, Tórshavn, Faroe Islands.
Eur J Neurol. 2022 Aug;29(8):2192-2200. doi: 10.1111/ene.15351. Epub 2022 Apr 19.
The Faroe Islands are a geographically isolated population in the North Atlantic with a similar prevalence of Alzheimer's disease (AD) and all-cause dementia as other European populations. However, the genetic risk underlying AD and other dementia susceptibility has yet to be elucidated.
Forty-nine single-nucleotide polymorphisms (SNPs) were genotyped in 174 patients with AD and other dementias and 159 healthy controls. Single variant and polygenic risk score (PRS) associations, with/without APOE variability, were assessed by logistic regression. Performance was examined using receiver operating characteristic area under the curve (ROC AUC) analysis.
APOErs429358 was associated with AD in the Faroese cohort after correction for multiple testing (odds ratio [OR] 6.32, 95% confidence interval [CI] 3.98-10.05, p = 6.31e ), with suggestive evidence for three other variants: NECTIN2 rs41289512 (OR 2.05, 95% CI 1.20-3.51, p = 0.01), HLA-DRB1 rs6931277 (OR 0.67, 95% CI 0.48-0.94, p = 0.02) and APOE rs7412 [ε2] (OR 0.28, 95% CI 0.11-0.73, p = 0.01). PRSs were associated with AD with or without the inclusion of APOE (PRS OR = 4.5, 95% CI 2.90-5.85, p = 4.56e , and PRS OR = 1.53, 95% CI 1.21-1.98, p = 6.82e ). AD ROC AUC analyses demonstrated a PRS AUC = 80.3% and PRS AUC = 63.4%. However, PRS was also significantly associated with all-cause dementia (OR = 3.39, 95% CI 2.51-4.71, p = 2.50e ) with an AUC = 76.9%, that is, all-cause dementia showed similar results albeit less significant.
In the Faroe Islands, SNP analyses highlighted APOE and immunogenomic variability in AD and dementia risk. PRS , based on 25 SNPs/loci, had excellent sensitivity and specificity for AD with an AUC of 80.3%. High PRSs were also associated with an earlier onset of late-onset AD.
法罗群岛是北大西洋中一个地理位置孤立的人群，其阿尔茨海默病（AD）和所有原因痴呆的患病率与其他欧洲人群相似。然而，AD 和其他痴呆易感性的遗传风险尚未阐明。
在 174 名 AD 患者和其他痴呆患者和 159 名健康对照中，对 49 个单核苷酸多态性（SNP）进行了基因分型。通过逻辑回归评估了带有/不带有 APOE 变异性的单变体和多基因风险评分（PRS）关联。使用接收者操作特征曲线（ROC AUC）分析来评估性能。
在对多个测试进行校正后，APOErs429358 与法罗群岛队列中的 AD 相关（比值比 [OR] 6.32，95%置信区间 [CI] 3.98-10.05，p = 6.31e），有三个其他变体的提示性证据：NECTIN2 rs41289512（OR 2.05，95%CI 1.20-3.51，p = 0.01），HLA-DRB1 rs6931277（OR 0.67，95%CI 0.48-0.94，p = 0.02）和 APOE rs7412 [ε2]（OR 0.28，95%CI 0.11-0.73，p = 0.01）。无论是否包含 APOE，PRS 均与 AD 相关（PRS OR = 4.5，95%CI 2.90-5.85，p = 4.56e）和 PRS OR = 1.53，95%CI 1.21-1.98，p = 6.82e）。AD 的 ROC AUC 分析表明 PRS AUC = 80.3%和 PRS AUC = 63.4%。然而，PRS 也与全因痴呆（OR = 3.39，95%CI 2.51-4.71，p = 2.50e）显着相关，AUC = 76.9%，即全因痴呆的结果相似，尽管不那么显着。
在法罗群岛，SNP 分析突出了 APOE 和免疫基因组变异性在 AD 和痴呆风险中的作用。基于 25 个 SNP/基因座的 PRS 对 AD 具有出色的敏感性和特异性，AUC 为 80.3%。高 PRS 也与晚发性 AD 的发病年龄较早有关。
