Exploring the relationship between socioeconomic deprivation index and Alzheimer's disease using summary-level data: From genetic correlation to causality

Abstract

Patients with Alzheimer's disease (AD) are markedly increasing as population aging and no disease-modifying therapies are currently available for AD. Previous studies suggested a broad link between socioeconomic status and a variety of disorders, including mental illness and cognitive abilities. However, the association between socioeconomic deprivation and AD has been unknown. We here employed Townsend deprivation index (TDI) to explore such relation and found a positive genetic correlation (r̂g=0.211, P = 8.00 × 10−4) between the two traits with summary statistics data (N = 455,258 for TDI and N = 455,815 for AD). Then, we performed pleiotropy analysis at both variant and gene levels using a powerful method called PLACO and detected 87 distinct pleiotropic genes. Functional analysis demonstrated these genes were significantly enriched in pancreas, liver, heart, blood, brain, and muscle tissues. Using Mendelian randomization methods, we further found that one genetically predicted standard deviation elevation in TDI could lead to approximately 18.5% (95% confidence intervals 1.6– 38.2%, P = 0.031) increase of AD risk, and that the identified causal association was robust against used MR approaches, horizontal pleiotropy, and instrumental selection. Overall, this study provides deep insight into common genetic components underlying TDI and AD, and further reveals causal connection between them. It is also helpful to develop a more suitable plan for ameliorating inequities, hardship, and disadvantage, with the hope of improving health outcomes among economically disadvantaged people.