Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study
dc.contributor.author | Zhang, N | |
dc.contributor.author | Ranson, JM | |
dc.contributor.author | Zheng, Z-J | |
dc.contributor.author | Hannon, E | |
dc.contributor.author | Zhou, Z | |
dc.contributor.author | Kong, X | |
dc.contributor.author | Llewellyn, DJ | |
dc.contributor.author | King, DA | |
dc.contributor.author | Huang, J | |
dc.date.accessioned | 2021-06-28T14:50:50Z | |
dc.date.issued | 2021-06-21 | |
dc.description.abstract | We evaluated whether the association between cigarette smoking and dementia risk is modified by genetic predisposition including apolipoprotein E (APOE) genotype and polygenic risk (excluding the APOE region). We included 193,198 UK Biobank participants aged 60-73 years without dementia at baseline. Of non-APOE-ε4 carriers, 0.89% (95% CI 0.73-1.08%) current smokers developed dementia compared with 0.49% (95% CI 0.44-0.55%) of never smokers (adjusted HR 1.78; 95% CI 1.39-2.29). In contrast, of one APOE-ε4 allele carriers, 1.69% (95% CI 1.31-2.12%) current smokers developed dementia compared with 1.40% (95% CI 1.25-1.55%) of never smokers (adjusted HR 1.06; 95% CI 0.77-1.45); of two APOE-ε4 alleles carriers, 4.90% (95% CI 2.92-7.61%) current smokers developed dementia compared with 3.87% (95% CI 3.11-4.74%) of never smokers (adjusted HR 0.94; 95% CI 0.49-1.79). Of participants with high polygenic risk, 1.77% (95% CI 1.35-2.27%) current smokers developed dementia compared with 1.05% (95% CI 0.91-1.21%) of never smokers (adjusted HR 1.63; 95% CI 1.16-2.28). A significant interaction was found between APOE genotype and smoking status (P = 0.002) while no significant interaction was identified between polygenic risk and smoking status (P = 0.25). APOE genotype but not polygenic risk modified the effect of smoking on dementia risk. | en_GB |
dc.description.sponsorship | National Key Research and Development Program of China | en_GB |
dc.description.sponsorship | Alzheimer’s Research UK | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.description.sponsorship | JP Moulton Foundation | en_GB |
dc.description.sponsorship | National Institute on Aging / National Institutes of Health | en_GB |
dc.description.sponsorship | Alan Turing Institute / Engineering and Physical Sciences Research Council | en_GB |
dc.identifier.citation | Vol. 11, article 12953 | en_GB |
dc.identifier.doi | 10.1038/s41598-021-92304-x | |
dc.identifier.grantnumber | 2020YFC2002900 | en_GB |
dc.identifier.grantnumber | RF1AG055654 | en_GB |
dc.identifier.grantnumber | EP/N510129/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/126224 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/34155245 | en_GB |
dc.rights | © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-06-28T14:50:50Z | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version. Available on open access from Nature Research via the DOI in this record | en_GB |
dc.description | Data availability: The data that support the findings of this study are available from the corresponding author on reasonable request. | en_GB |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.journal | Scientific Reports | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2021-06-03 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-06-21 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-06-28T14:46:34Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2021-06-28T14:51:43Z | |
refterms.panel | A | en_GB |
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