Polygenic risk of Alzheimer's disease in the Faroe Islands
Abstract 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...
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crwiley:10.1111/ene.15351 2024-06-02T08:06:23+00:00 Polygenic risk of Alzheimer's disease in the Faroe Islands Johansen, Malan Joensen, Sofus Restorff, Marjun Stórá, Tórmóður Christy, Darren Gustavsson, Emil K. Bian, Jiang Guo, Yi Farrer, Matthew J. Petersen, Maria Skaalum Hartmann Fonden 2022 http://dx.doi.org/10.1111/ene.15351 https://onlinelibrary.wiley.com/doi/pdf/10.1111/ene.15351 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ene.15351 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor European Journal of Neurology volume 29, issue 8, page 2192-2200 ISSN 1351-5101 1468-1331 journal-article 2022 crwiley https://doi.org/10.1111/ene.15351 2024-05-03T11:54:44Z Abstract 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 APOE rs429358 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. Article in Journal/Newspaper Faroe Islands North Atlantic Wiley Online Library Faroe Islands European Journal of Neurology 29 8 2192 2200 |
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Wiley Online Library |
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English |
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Abstract 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 APOE rs429358 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. |
author2 |
Hartmann Fonden |
format |
Article in Journal/Newspaper |
author |
Johansen, Malan Joensen, Sofus Restorff, Marjun Stórá, Tórmóður Christy, Darren Gustavsson, Emil K. Bian, Jiang Guo, Yi Farrer, Matthew J. Petersen, Maria Skaalum |
spellingShingle |
Johansen, Malan Joensen, Sofus Restorff, Marjun Stórá, Tórmóður Christy, Darren Gustavsson, Emil K. Bian, Jiang Guo, Yi Farrer, Matthew J. Petersen, Maria Skaalum Polygenic risk of Alzheimer's disease in the Faroe Islands |
author_facet |
Johansen, Malan Joensen, Sofus Restorff, Marjun Stórá, Tórmóður Christy, Darren Gustavsson, Emil K. Bian, Jiang Guo, Yi Farrer, Matthew J. Petersen, Maria Skaalum |
author_sort |
Johansen, Malan |
title |
Polygenic risk of Alzheimer's disease in the Faroe Islands |
title_short |
Polygenic risk of Alzheimer's disease in the Faroe Islands |
title_full |
Polygenic risk of Alzheimer's disease in the Faroe Islands |
title_fullStr |
Polygenic risk of Alzheimer's disease in the Faroe Islands |
title_full_unstemmed |
Polygenic risk of Alzheimer's disease in the Faroe Islands |
title_sort |
polygenic risk of alzheimer's disease in the faroe islands |
publisher |
Wiley |
publishDate |
2022 |
url |
http://dx.doi.org/10.1111/ene.15351 https://onlinelibrary.wiley.com/doi/pdf/10.1111/ene.15351 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ene.15351 |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands North Atlantic |
genre_facet |
Faroe Islands North Atlantic |
op_source |
European Journal of Neurology volume 29, issue 8, page 2192-2200 ISSN 1351-5101 1468-1331 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1111/ene.15351 |
container_title |
European Journal of Neurology |
container_volume |
29 |
container_issue |
8 |
container_start_page |
2192 |
op_container_end_page |
2200 |
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1800751326057988096 |