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

Autor: Johansen M; 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., Joensen S; Psychiatric Center, Dementia Clinic, National Hospital of the Faroe Islands, Tórshavn, Faroe Islands., Restorff M; Psychiatric Center, Dementia Clinic, National Hospital of the Faroe Islands, Tórshavn, Faroe Islands., Stórá T; Psychiatric Center, Dementia Clinic, National Hospital of the Faroe Islands, Tórshavn, Faroe Islands., Christy D; Centre for Applied Neurogenetics, University of British Columbia, Vancouver, BC, Canada., Gustavsson EK; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.; Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK., Bian J; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA., Guo Y; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA., Farrer MJ; Centre for Applied Neurogenetics, University of British Columbia, Vancouver, BC, Canada.; Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA., Petersen MS; 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.
Jazyk: angličtina
Zdroj: European journal of neurology [Eur J Neurol] 2022 Aug; Vol. 29 (8), pp. 2192-2200. Date of Electronic Publication: 2022 Apr 19.
DOI: 10.1111/ene.15351
Abstrakt: 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.
(© 2022 European Academy of Neurology.)
Databáze: MEDLINE
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