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Mendelian randomization study of diabetes and dementia in the Million Veteran Program

Title: Mendelian randomization study of diabetes and dementia in the Million Veteran Program
Authors: Litkowski, Elizabeth M.; Logue, Mark W.; Zhang, Rui; Charest, Brian R.; Lange, Ethan M.; Hokanson, John E.; Lynch, Julie A.; Vujkovic, Marijana; Phillips, Lawrence S.; Hauger, Richard L.; Lange, Leslie A.; Raghavan, Sridharan
Contributors: National Institutes of Health; Cystic Fibrosis Foundation
Source: Alzheimer's & Dementia ; volume 19, issue 10, page 4367-4376 ; ISSN 1552-5260 1552-5279
Publisher Information: Wiley
Publication Year: 2023
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: Introduction Diabetes and dementia are diseases of high health‐care burden worldwide. Individuals with diabetes have 1.4 to 2.2 times higher risk of dementia. Our objective was to evaluate evidence of causality between these two common diseases. Methods We conducted a one‐sample Mendelian randomization (MR) analysis in the US Department of Veterans Affairs Million Veteran program. The study included 334,672 participants ≥65 years of age with type 2 diabetes and dementia case‐control status and genotype data. Results For each standard deviation increase in genetically predicted diabetes, we found increased odds of three dementia diagnoses in non‐Hispanic White participants (all‐cause: odds ratio [OR] = 1.07 [1.05–1.08], P = 3.40E‐18; vascular: OR = 1.11 [1.07–1.15], P = 3.63E‐09, Alzheimer's disease [AD]: OR = 1.06 [1.02–1.09], P = 6.84E‐04) and non‐Hispanic Black participants (all‐cause: OR = 1.06 [1.02–1.10], P = 3.66E‐03, vascular: OR = 1.11 [1.04–1.19], P = 2.20E‐03, AD: OR = 1.12 [1.02–1.23], P = 1.60E‐02) but not in Hispanic participants (all P > 0.05). Discussion We found evidence of causality between diabetes and dementia using a one‐sample MR study, with access to individual level data, overcoming limitations of prior studies using two‐sample MR techniques.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1002/alz.13373
Availability: https://doi.org/10.1002/alz.13373
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
Accession Number: edsbas.AD803A27
Database: BASE