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.

Trend in the Incidence and Prevalence of Dementia in the Faroe Islands.

BACKGROUND: Dementia has become an important public health, economic, and social issue. Knowledge about prevalence, incidence, and trends of dementia in a country is of crucial importance. However, no studies of incidence or prevalence of dementia have been undertaken in the Faroe Islands. OBJECTIVES: The aim was to estimate the overall and trend in incidence and prevalence of dementia among individuals ≥60 years in the Faroe Islands from 2010-2017. METHODS: Population-based register study where all individuals ≥60 years with a dementia diagnosis from January 2010 to December 2017 were identified. The overall crude and age-and-sex-specific incidence and prevalence was assessed. RESULTS: The overall crude incidence among individuals ≥60 years from 2010 to 2017 was 5.1 per 1000 individuals and the prevalence 22.5 per 1000 individuals. The age-and sex-standardized annual incidence of dementia fluctuated between 4.8 and 6.7 per 1000, with no clear secular trend while the age-and sex-standardized prevalence increased steadily from 14.5 in 2010 to 30.8 per 1000 individuals in 2017. CONCLUSION: The age-standardized incidence or prevalence estimates in the Faroes seem to be lower than in other countries. The incidence was relatively stable in the period while the prevalence of dementia simultaneously increased.

A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene.

Panic disorder (PD) is a mental disorder with recurrent panic attacks that occur spontaneously and are not associated to any particular object or situation. There is no consensus on what causes PD. However, it is recognized that PD is influenced by environmental factors, as well as genetic factors. Despite a significant hereditary component, genetic studies have only been modestly successful in identifying genes of importance for the development of PD. In this study, we conducted a genome-wide scan using microsatellite markers and PD patients and control individuals from the isolated population of the Faroe Islands. Subsequently, we conducted a fine mapping, which revealed the amiloride-sensitive cation channel 1 (ACCN1) located on chromosome 17q11.2-q12 as a potential candidate gene for PD. The further analyses of the ACCN1 gene using single-nucleotide polymorphisms (SNPs) revealed significant association with PD in an extended Faroese case-control sample. However, analyses of a larger independent Danish case-control sample yielded no substantial significant association. This suggests that the possible risk alleles associated in the isolated population are not those involved in the development of PD in a larger outbred population.