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dc.contributor.authorLarsson, Susanna Cen
dc.contributor.authorTraylor, Matthewen
dc.contributor.authorMalik, Raineren
dc.contributor.authorDichgans, Martinen
dc.contributor.authorBurgess, Stephenen
dc.contributor.authorMarkus, Hughen
dc.contributor.authorCoSTREAM Consortium, on behalf of the International Genomics of Alzheimer’s Project,en
dc.description.abstractOBJECTIVE: To determine which potentially modifiable risk factors, including socioeconomic, lifestyle/dietary, cardiometabolic, and inflammatory factors, are associated with Alzheimer's disease. DESIGN: Mendelian randomisation study using genetic variants associated with the modifiable risk factors as instrumental variables. SETTING: International Genomics of Alzheimer's Project. PARTICIPANTS: 17 008 cases of Alzheimer's disease and 37 154 controls. MAIN OUTCOME MEASURES: Odds ratio of Alzheimer's per genetically predicted increase in each modifiable risk factor estimated with Mendelian randomisation analysis. RESULTS: This study included analyses of 24 potentially modifiable risk factors. A Bonferroni corrected threshold of P=0.002 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. Genetically predicted educational attainment was significantly associated with Alzheimer's. The odds ratios were 0.89 (95% confidence interval 0.84 to 0.93; P=2.4×10-6) per year of education completed and 0.74 (0.63 to 0.86; P=8.0×10-5) per unit increase in log odds of having completed college/university. The correlated trait intelligence had a suggestive association with Alzheimer's (per genetically predicted 1 SD higher intelligence: 0.73, 0.57 to 0.93; P=0.01). There was suggestive evidence for potential associations between genetically predicted higher quantity of smoking (per 10 cigarettes a day: 0.69, 0.49 to 0.99; P=0.04) and 25-hydroxyvitamin D concentrations (per 20% higher levels: 0.92, 0.85 to 0.98; P=0.01) and lower odds of Alzheimer's and between higher coffee consumption (per one cup a day: 1.26, 1.05 to 1.51; P=0.01) and higher odds of Alzheimer's. Genetically predicted alcohol consumption, serum folate, serum vitamin B12, homocysteine, cardiometabolic factors, and C reactive protein were not associated with Alzheimer's disease. CONCLUSION: These results provide support that higher educational attainment is associated with a reduced risk of Alzheimer's disease.
dc.rightsAttribution 4.0 International*
dc.subjectCoSTREAM Consortium, on behalf of the International Genomics of Alzheimer’s Projecten
dc.subjectAlzheimer Diseaseen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectOdds Ratioen
dc.subjectRisk Factorsen
dc.subjectLife Styleen
dc.subjectEducational Statusen
dc.subjectMendelian Randomization Analysisen
dc.titleModifiable pathways in Alzheimer's disease: Mendelian randomisation analysis.en
prism.publicationNameBMJ (Clinical research ed.)en
dc.contributor.orcidLarsson, Susanna C [0000-0003-0118-0341]
dc.contributor.orcidTraylor, Matthew [0000-0001-6624-8621]
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.contributor.orcidMarkus, Hugh [0000-0002-9794-5996]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (667375)
pubs.funder-project-idBritish Heart Foundation (RG/16/4/32218)
pubs.funder-project-idMRC (MR/L003120/1)
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
pubs.funder-project-idBritish Heart Foundation (RG/08/014/24067)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International