The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)

dc.contributorHáskóli Íslandsen_US
dc.contributorUniversity of Icelanden_US
dc.contributor.authorWolters, Frank J.
dc.contributor.authorYang, Qiong
dc.contributor.authorBiggs, Mary L.
dc.contributor.authorJakobsdottir, Johanna
dc.contributor.authorLi, Shuo
dc.contributor.authorEvans, Daniel S.
dc.contributor.authorBis, Joshua C.
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorZilhao, Nuno R.
dc.contributor.authorGhanbari, Mohsen
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorLauner, Lenore
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorTranah, Gregory J.
dc.contributor.authorKulminski, Alexander M.
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorSeshadri, Sudha
dc.contributor.departmentLæknadeild (HÍ)en_US
dc.contributor.departmentFaculty of Medicine (UI)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.date.accessioned2020-08-13T11:16:50Z
dc.date.available2020-08-13T11:16:50Z
dc.date.issued2019-07-29
dc.descriptionPublisher's version (útgefin grein)en_US
dc.description.abstractBackground Apolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-e4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-e2 allele on diseases in the elderly and survival remains elusive. Methods We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-e2, with survival in the population. Results During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-e3 carriers, APOE-e2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1∗10-2), whereas APOE-e4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8∗10-16). APOE was associated with mortality risk in a dose-dependent manner, with risk estimates lowest for homozygous APOE-e2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-e4 (HR 1.52,1.37- 1.70). After censoring for dementia, effect estimates remained similar for APOE-e2 (HR 0.95,0.90-1.01), but attenuated for APOE-e4 (HR 1.07,1.01-1.12). Results were broadly similar across cohorts, and did not differ by age or sex. APOE genotype was associated with baseline lipid fractions (e.g. mean difference(95%CI) in LDL(mg/dL) for e2 versus e33: -17.1(-18.1-16.0), and e4 versus e33: +5.7(4.8;6.5)), but the association between APOE and mortality was unaltered after adjustment for baseline LDL or cardiovascular disease. Given the European ancestry of the study population, results may not apply to other ethnicities. Conclusion Compared with APOE-e3, APOE-e2 is associated with prolonged survival, whereas mortality risk is increased for APOE-e4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-e2 in health and disease.en_US
dc.description.sponsorshipInfrastructure for the CHARGE Consortium members in this grant is supported in part by the National Heart, Lung, and Blood Institute (NHLBI, http://www.nhlbi.nih.gov) grant HL105756 (Psaty) and AG033193 (Seshadri). This work was also supported by a grant from the Consortium to Study the Genetics of Longevity (U19AG023122; PI Cummings; subproject title ‘APOE2 Genotype in Longevity and Healthy Aging’, PI: Seshadri). Detailed funding information for all studies that contributed to this work are provided in the online Appendix funding section (S5 Supporting information). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.description.versionPeer Revieweden_US
dc.format.extente0219668en_US
dc.identifier.citationWolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, et al. (2019) The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE). PLoS ONE 14(7): e0219668. https://doi.org/10.1371/journal.pone.0219668en_US
dc.identifier.doi10.1371/journal.pone.0219668
dc.identifier.issn1932-6203
dc.identifier.journalPlos Oneen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/1986
dc.language.isoenen_US
dc.publisherPublic Library of Science (PLoS)en_US
dc.relation.ispartofseriesPlos One;14(7)
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0219668en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectApolipoprotein Een_US
dc.subjectGlycoproteinen_US
dc.subjectLipiden_US
dc.subjectLipoproteinen_US
dc.subjectErfðarannsókniren_US
dc.subjectFituefnien_US
dc.subjectPrótínen_US
dc.titleThe impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)en_US
dc.typeinfo:eu-repo/semantics/articleen_US
dcterms.licenseThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US

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