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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/444| A non-APOE polygenic score for Alzheimer's disease and APOE-ε4 have independent associations with dementia in the Health and Retirement Study | |
| Kelly S. Benke Erin B Ware Harita S Vadari Jessica D. Faul Steven G Heeringa Kenneth M Langa Jennifer A. Smith Jennifer J. Manly Colter M Mitchell Sharon LR Kardia Kelly M Bakulski | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución-SinDerivadas | |
| 10.1101/2020.02.10.20021667 | |
| INTRODUCTION. Alzheimer's disease (AD) is a common and costly neurodegenerative disorder. A large proportion of risk is heritable and many genetic risk factors for AD have been identified. The cumulative genetic risk of known markers has not been benchmarked for dementia in a population-based sample. METHODS. In the United States population-based Health and Retirement Study (HRS) (waves 1995-2014), we evaluated the role of cumulative genetic risk for AD, with and without the APOE -ε 4 alleles, on dementia status (dementia, cognitive impairment without dementia, borderline cognitive impairment without dementia, cognitively normal). We used logistic regression, accounting for demographic covariates and genetic principal components, and analyses were stratified by European and African genetic ancestry. RESULTS. In the European ancestry sample (n=8399), both AD polygenic score excluding the APOE genetic region (odds ratio (OR)=1.10; 95% confidence interval (CI): 1.00, 1.20) and the presence of any APOE -ε 4 alleles (OR=2.42; 95% CI: 1.99, 2.95) were associated with the odds of dementia relative to normal cognition in a mutually-adjusted model. In the African ancestry sample (n=1605), the presence of any APOE -ε 4 alleles was associated with 1.77 (95% CI: 1.20, 2.61) times higher odds of dementia, while the AD polygenic score excluding the APOE genetic region was not significantly associated with the odds of dementia relative to normal cognition 1.06 (95% CI: 0.97, 1.30). DISCUSSION. Cumulative genetic risk for AD and APOE -ε 4 are both independent predictors of dementia. This study provides important insight into the polygenic nature of dementia and demonstrates the utility of polygenic scores in dementia research. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Institutes of Health (grant numbers R01 AG055406, R01 AG055654, R25 AG053227, R01 AG053972, R03 AG048806). The Health and Retirement Study is sponsored by the National Institute on Aging (U01 AG009740) and is conducted at the Institute for Social Research, University of Michigan. ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data are publicly available https://hrs.isr.umich.edu/about <https://hrs.isr.umich.edu/about> | |
| Cold Spring Harbor Laboratory Press | |
| 2020 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/2020.02.10.20021667v2 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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