Polygenic risk of Alzheimer's disease in the Faroe Islands.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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-15 ), 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+APOE OR = 4.5, 95% CI 2.90-5.85, p = 4.56e-15 , and PRS-APOE OR = 1.53, 95% CI 1.21-1.98, p = 6.82e-4 ). AD ROC AUC analyses demonstrated a PRS+APOE AUC = 80.3% and PRS-APOE AUC = 63.4%. However, PRS+APOE was also significantly associated with all-cause dementia (OR = 3.39, 95% CI 2.51-4.71, p = 2.50e-14 ) with an AUC = 76.9%, that is, all-cause dementia showed similar results albeit less significant. DISCUSSION: In the Faroe Islands, SNP analyses highlighted APOE and immunogenomic variability in AD and dementia risk. PRS+APOE , 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.

High incidence of amyotrophic lateral sclerosis in the Faroe Islands 2010-2020.

The Faroese population isolate harbors epidemiological and genetic characteristics that likely differ from outbred populations. This population-based register study found that the Faroese 2010-2020 crude incidence of amyotrophic lateral sclerosis (ALS) was 4.9/100,000 person-years (95% confidence interval [CI], 3.3-7.0) and the age- and sex-standardized incidence (US 2010 Census Population) was 4.1/100,000 person-years (95% CI, 2.7-6.0), which is a 68% increase from the 1987-2009 estimate. The 2020 crude prevalence was 9.5/100,000 (95% CI, 3.0-19.6) in a population of 52,912 inhabitants. Incidence and prevalence estimates of ALS in the Faroes are high and further research is warranted to uncover the genetic or environmental determinants of ALS in this population.

Low Seroprevalence among Undetected COVID-19 Cases, Faroe Islands, November 2020.

We conducted a second nationwide severe acute respiratory syndrome coronavirus 2 seroprevalence study in the Faroe Islands during November 2020. We found crude seroprevalence was 0.3% and prevalence was 0.4% after adjusting for test sensitivity and specificity. This low seroprevalence supports the prevention strategies used in the Faroe Islands.

Amyotrophic lateral sclerosis in the Faroe Islands - a genealogical study.

In the Faroe Islands, a clustering of amyotrophic lateral sclerosis (ALS) was observed on the geographically isolated island, Suðuroy. This study aims to estimate the frequency of familial ALS (fALS) in the Faroes including 43 patients diagnosed with ALS. Patients with fALS were identified through medical records and the Faroese Multi Generation Register. Firstly, fALS was recognized when occurring between first- or second-degree relatives. Secondly, families and individuals with fALS were recognized through pedigrees (≥3 cases within 3 generations). The prevalence of ALS was 3 times higher in Suðuroy compared to the nationwide prevalence. The frequency of fALS was at least 14% (n = 6) and mean survival time was 1.7 years shorter for fALS compared to sporatic ALS (p = 0.01. SD = 0.5, range 1.0-2.2). This study is suggestive of familial clustering in excess of expected for ALS and supports a genetic contribution to ALS in the Faroe Islands albeit environmental exposure within families cannot be excluded.

Seroprevalence of SARS-CoV-2-Specific Antibodies, Faroe Islands.

We conducted a nationwide study of the prevalence of severe acute respiratory syndrome coronavirus 2 infection in the Faroe Islands. Of 1,075 randomly selected participants, 6 (0.6%) tested seropositive for antibodies to the virus. Adjustment for test sensitivity and specificity yielded a 0.7% prevalence. Our findings will help us evaluate our public health response.