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

Abstract

Structured AbstractINTRODUCTIONDiabetes and dementia are diseases of high healthcare 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.METHODSWe conducted a one-sample Mendelian randomization (MR) analysis in the U.S. 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.RESULTSFor each standard deviation increase in genetically-predicted diabetes, we found increased odds of three dementia diagnoses in non-Hispanic White participants (all-cause: 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: 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, Alzheimer’s: OR=1.12 [1.02-1.23],P=1.60E-02) but not in Hispanic participants (allP>.05).DISCUSSIONWe 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 utilizing two-sample MR techniques.