Introduction: We investigated associations of obesity with the expression of Alzheimer's disease (AD)-related genes in a large community-based cohort.
Methods: The sample consisted of 5619 participants from the Framingham Heart Study. Obesity metrics included body mass index (BMI) and waist-to-hip ratio (WHR). Gene expression was measured for a set of 74 AD-related genes, derived by integrating genome-wide association study results with functional genomics data.
Results: Obesity metrics were associated with the expression of 21 AD-related genes. The strongest associations were observed with CLU, CD2AP, KLC3, and FCER1G. Unique associations were noted with TSPAN14, SLC24A4 for BMI, and ZSCAN21, BCKDK for WHR. After adjustment for cardiovascular risk factors, 13 associations remained significant for BMI and 8 for WHR. Dichotomous obesity metrics exhibited unique associations with EPHX2 for BMI, and with TSPAN14 for WHR.
Discussion: Obesity was associated with AD-related gene expression; these findings shed light on the molecular pathways linking obesity to AD.
Keywords: Alzheimer's disease; dementia; functional genomics; gene expression; genome-wide association study; obesity.
© 2023 the Alzheimer's Association.